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1.  The IMGT/HLA database 
Nucleic Acids Research  2012;41(Database issue):D1222-D1227.
It is 14 years since the IMGT/HLA database was first released, providing the HLA community with a searchable repository of highly curated HLA sequences. The HLA complex is located within the 6p21.3 region of human chromosome 6 and contains more than 220 genes of diverse function. Of these, 21 genes encode proteins of the immune system that are highly polymorphic. The naming of these HLA genes and alleles and their quality control is the responsibility of the World Health Organization Nomenclature Committee for Factors of the HLA System. Through the work of the HLA Informatics Group and in collaboration with the European Bioinformatics Institute, we are able to provide public access to these data through the website http://www.ebi.ac.uk/imgt/hla/. Regular updates to the website ensure that new and confirmatory sequences are dispersed to the HLA community and the wider research and clinical communities. This article describes the latest updates and additional tools added to the IMGT/HLA project.
doi:10.1093/nar/gks949
PMCID: PMC3531221  PMID: 23080122
2.  The IMGT/HLA database 
Nucleic Acids Research  2008;37(Database issue):D1013-D1017.
It is 10 years since the IMGT/HLA database was released, providing the HLA community with a searchable repository of highly curated HLA sequences. The HLA complex is located within the 6p21.3 region of human chromosome 6 and contains more than 220 genes of diverse function. Many of the genes encode proteins of the immune system and are highly polymorphic. The naming of these HLA genes and alleles, and their quality control is the responsibility of the WHO Nomenclature Committee for Factors of the HLA System. Through the work of the HLA Informatics Group and in collaboration with the European Bioinformatics Institute, we are able to provide public access to this data through the website http://www.ebi.ac.uk/imgt/hla/. The first release contained 964 sequences, the most recent release 3300 sequences, with around 450 new sequences been added each year. The tools provided on the website have been updated to allow more complex alignments, which include genomic sequence data, as well as the development of tools for probe and primer design and the inclusion of data from the HLA Dictionary. Regular updates to the website ensure that new and confirmatory sequences are dispersed to the HLA community, and the wider research and clinical communities.
doi:10.1093/nar/gkn662
PMCID: PMC2686596  PMID: 18838392
3.  IMGT/HLA Database—a sequence database for the human major histocompatibility complex 
Nucleic Acids Research  2001;29(1):210-213.
The IMGT/HLA Database (www.ebi.ac.uk/imgt/hla/) specialises in sequences of polymorphic genes of the HLA system, the human major histocompatibility complex (MHC). The HLA complex is located within the 6p21.3 region on the short arm of human chromosome 6 and contains more than 220 genes of diverse function. Many of the genes encode proteins of the immune system and these include the 21 highly polymorphic HLA genes, which influence the outcome of clinical transplantation and confer susceptibility to a wide range of non-infectious diseases. The database contains sequences for all HLA alleles officially recognised by the WHO Nomenclature Committee for Factors of the HLA System and provides users with online tools and facilities for their retrieval and analysis. These include allele reports, alignment tools and detailed descriptions of the source cells. The online IMGT/HLA submission tool allows both new and confirmatory sequences to be submitted directly to the WHO Nomenclature Committee. The latest version (release 1.7.0 July 2000) contains 1220 HLA alleles derived from over 2700 component sequences from the EMBL/GenBank/DDBJ databases. The HLA database provides a model which will be extended to provide specialist databases for polymorphic MHC genes of other species.
PMCID: PMC29780  PMID: 11125094
4.  IMGT/HLA and IMGT/MHC: sequence databases for the study of the major histocompatibility complex 
Nucleic Acids Research  2003;31(1):311-314.
The IMGT/HLA database (http://www.ebi.ac.uk/imgt/hla) has provided a centralized repository for the sequences of the alleles named by the WHO Nomenclature Committee for Factors of the HLA System for the past four years. Since its initial release the database has grown and is the primary source of information for the study of sequences of the human major histocompatibilty complex. The initial release of the database contained a limited number of tools. As a result of feedback from our users and developments in HLA we have been able to provide new tools and facilities. The HLA sequences have also been extended to include intron sequences and the 3′ and 5′ untranslated regions in the alignments and also the inclusion of new genes such as MICA. The IMGT/MHC database (http://www.ebi.ac.uk/imgt/mhc) was released in March 2002 to provide a similar resource for other species. The first release of IMGT/MHC contains the sequences of non-human primates (apes, new and old world monkeys), canines and feline sequences. Further species will be added shortly and the database aims to become the primary source of MHC data for non-human sequences.
PMCID: PMC165517  PMID: 12520010
5.  IMGT, the international ImMunoGeneTics database. 
Nucleic Acids Research  1997;25(1):206-211.
IMGT, the international ImMunoGeneTics database, is an integrated database specializing in immunoglobulins, T-cell receptors (TcR) and major histocompatibility complex (MHC) of all vertebrate species, initiated and co-ordinated by Marie-Paule Lefranc, CNRS, Montpellier II University, Montpellier, France (lefranc@ligm.crbm.cnrs-mop.fr). IMGT includes two databases: LIGM-DB (for immunoglobulins and TcR) and MHC/HLA-DB. IMGT comprises expertly annotated sequences and alignment tables. LIGM-DB contains more than 19 000 immunoglobulin and TcR sequences from 78 species. MHC/HLA-DB contains class I and class II human leukocyte antigen alignment tables. An IMGT tool, DNAPLOT, developed for immunoglobulins, TcR and MHC sequence alignments, is also available. IMGT works in close collaboration with the EMBL database. IMGT goals are to establish a common data access to all immunogenetics data, including sequences, oligonucleotide primers, gene maps and other genetic data of immunoglobulins, TcR and MHC molecules, and to provide a graphical user-friendly data access. IMGT will have important implications in medical research (repertoire in autoimmune diseases, AIDS, leukemias, lymphomas), therapeutical approaches (antibody engineering), genome diversity and genome evolution studies. IMGT can be accessed at http://imgt.cnusc.fr:8104 and http://www.ebi.ac.uk/IMGT
PMCID: PMC146384  PMID: 9016537
6.  Common and Well-Documented HLA Alleles: 2012 Update to the CWD Catalogue 
Tissue antigens  2013;81(4):194-203.
We have updated the catalogue of common and well-documented (CWD) HLA alleles to reflect current understanding of the prevalence of specific allele sequences. The original CWD catalogue designated 721 alleles at the HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, and –DPB1 loci in IMGT/HLA Database release 2.15.0 as being CWD. The updated CWD catalogue designates 1122 alleles at the HLA-A, -B, -C, -DRB1, -DRB3/4/5, -DQA1, -DQB1, -DPA1 and –DPB1 loci as being CWD, and represents 14.3% of the HLA alleles in IMGT/HLA Database release 3.9.0. In particular, we identified 415 of these alleles as being “common” (having known frequencies) and 707 as being “well-documented” on the basis of ~140,000 sequence-based typing observations and available HLA haplotype data. Using these allele prevalence data, we have also assigned CWD status to specific G and P designations. We identified 147/151 G groups and 290/415 P groups as being CWD. The CWD catalogue will be updated on a regular basis moving forward, and will incorporate changes to the IMGT/HLA Database as well as empirical data from the histocompatibility and immunogenetics community. This version 2.0.0 of the CWD catalogue is available online at cwd.immunogenomics.org, and will be integrated into the Allele Frequencies Net Database, the IMGT/HLA Database and National Marrow Donor Program’s bioinformatics web pages.
doi:10.1111/tan.12093
PMCID: PMC3634360  PMID: 23510415
allele prevalence; common allele; CWD; HLA; sequence based typing; well-documented allele
7.  Immunoglobulins: 25 Years of Immunoinformatics and IMGT-ONTOLOGY 
Biomolecules  2014;4(4):1102-1139.
IMGT®, the international ImMunoGeneTics information system® (CNRS and Montpellier University) is the global reference in immunogenetics and immunoinformatics. By its creation in 1989, IMGT® marked the advent of immunoinformatics, which emerged at the interface between immunogenetics and bioinformatics. IMGT® is specialized in the immunoglobulins (IG) or antibodies, T cell receptors (TR), major histocompatibility (MH), and IgSF and MhSF superfamilies. IMGT® has been built on the IMGT-ONTOLOGY axioms and concepts, which bridged the gap between genes, sequences and three-dimensional (3D) structures. The concepts include the IMGT® standardized keywords (identification), IMGT® standardized labels (description), IMGT® standardized nomenclature (classification), IMGT unique numbering and IMGT Colliers de Perles (numerotation). IMGT® comprises seven databases, 15,000 pages of web resources and 17 tools. IMGT® tools and databases provide a high-quality analysis of the IG from fish to humans, for basic, veterinary and medical research, and for antibody engineering and humanization. They include, as examples: IMGT/V-QUEST and IMGT/JunctionAnalysis for nucleotide sequence analysis and their high-throughput version IMGT/HighV-QUEST for next generation sequencing, IMGT/DomainGapAlign for amino acid sequence analysis of IG domains, IMGT/3Dstructure-DB for 3D structures, contact analysis and paratope/epitope interactions of IG/antigen complexes, and the IMGT/mAb-DB interface for therapeutic antibodies and fusion proteins for immunological applications (FPIA).
doi:10.3390/biom4041102
PMCID: PMC4279172  PMID: 25521638
IMGT; immunogenetics; immunoinformatics; IMGT-ONTOLOGY; IMGT Collier de Perles; immunoglobulin; immune repertoire; IMGT unique numbering; next generation sequencing; antibody humanization
8.  Immunoglobulin and T Cell Receptor Genes: IMGT® and the Birth and Rise of Immunoinformatics 
IMGT®, the international ImMunoGeneTics information system®1, (CNRS and Université Montpellier 2) is the global reference in immunogenetics and immunoinformatics. By its creation in 1989, IMGT® marked the advent of immunoinformatics, which emerged at the interface between immunogenetics and bioinformatics. IMGT® is specialized in the immunoglobulins (IG) or antibodies, T cell receptors (TR), major histocompatibility (MH), and proteins of the IgSF and MhSF superfamilies. IMGT® has been built on the IMGT-ONTOLOGY axioms and concepts, which bridged the gap between genes, sequences, and three-dimensional (3D) structures. The concepts include the IMGT® standardized keywords (concepts of identification), IMGT® standardized labels (concepts of description), IMGT® standardized nomenclature (concepts of classification), IMGT unique numbering, and IMGT Colliers de Perles (concepts of numerotation). IMGT® comprises seven databases, 15,000 pages of web resources, and 17 tools, and provides a high-quality and integrated system for the analysis of the genomic and expressed IG and TR repertoire of the adaptive immune responses. Tools and databases are used in basic, veterinary, and medical research, in clinical applications (mutation analysis in leukemia and lymphoma) and in antibody engineering and humanization. They include, for example IMGT/V-QUEST and IMGT/JunctionAnalysis for nucleotide sequence analysis and their high-throughput version IMGT/HighV-QUEST for next-generation sequencing (500,000 sequences per batch), IMGT/DomainGapAlign for amino acid sequence analysis of IG and TR variable and constant domains and of MH groove domains, IMGT/3Dstructure-DB for 3D structures, contact analysis and paratope/epitope interactions of IG/antigen and TR/peptide-MH complexes and IMGT/mAb-DB interface for therapeutic antibodies and fusion proteins for immune applications (FPIA).
doi:10.3389/fimmu.2014.00022
PMCID: PMC3913909  PMID: 24600447
IMGT; immunogenetics; immunoinformatics; IMGT-ONTOLOGY; IMGT Collier de Perles; immunoglobulin; T cell receptor; major histocompatibility
9.  IMGT/3Dstructure-DB and IMGT/DomainGapAlign: a database and a tool for immunoglobulins or antibodies, T cell receptors, MHC, IgSF and MhcSF 
Nucleic Acids Research  2009;38(Database issue):D301-D307.
IMGT/3Dstructure-DB is the three-dimensional (3D) structure database of IMGT®, the international ImMunoGenetics information system® that is acknowledged as the global reference in immunogenetics and immunoinformatics. IMGT/3Dstructure-DB contains 3D structures of immunoglobulins (IG) or antibodies, T cell receptors (TR), major histocompatibility complex (MHC) proteins, antigen receptor/antigen complexes (IG/Ag, TR/peptide/MHC) of vertebrates; 3D structures of related proteins of the immune system (RPI) of vertebrates and invertebrates, belonging to the immunoglobulin and MHC superfamilies (IgSF and MhcSF, respectively) and found in complexes with IG, TR or MHC. IMGT/3Dstructure-DB data are annotated according to the IMGT criteria, using IMGT/DomainGapAlign, and based on the IMGT-ONTOLOGY concepts and axioms. IMGT/3Dstructure-DB provides IMGT gene and allele identification (CLASSIFICATION), region and domain delimitations (DESCRIPTION), amino acid positions according to the IMGT unique numbering (NUMEROTATION) that are used in IMGT/3Dstructure-DB cards, results of contact analysis and renumbered flat files. In its Web version, the IMGT/DomainGapAlign tool analyses amino acid sequences, per domain. Coupled to the IMGT/Collier-de-Perles tool, it provides an invaluable help for antibody engineering and humanization design based on complementarity determining region (CDR) grafting as it precisely defines the standardized framework regions (FR-IMGT) and CDR-IMGT. IMGT/3Dstructure-DB and IMGT/DomainGapAlign are freely available at http://www.imgt.org.
doi:10.1093/nar/gkp946
PMCID: PMC2808948  PMID: 19900967
10.  IMGT, the international ImMunoGeneTics database® 
Nucleic Acids Research  2003;31(1):307-310.
The international ImMunoGeneTics database® (IMGT) (http://imgt.cines.fr), is a high quality integrated information system specializing in Immunoglobulins (IG), T cell Receptors (TR) and Major Histocompatibility Complex (MHC) of human and other vertebrates, created in 1989, by the Laboratoire d'ImmunoGénétique Moléculaire (LIGM), at the Université Montpellier II, CNRS, Montpellier, France. IMGT provides a common access to standardized data which include nucleotide and protein sequences, oligonucleotide primers, gene maps, genetic polymorphisms, specificities, 2D and 3D structures. IMGT includes three sequence databases (IMGT/LIGM-DB, IMGT/MHC-DB, IMGT/PRIMER-DB), one genome database (IMGT/GENE-DB) with different interfaces (IMGT/GeneSearch, IMGT/GeneView, IMGT/LocusView), one 3D structure database (IMGT/3Dstructure-DB), Web resources comprising 8000 HTML pages (‘IMGT Marie-Paule page’) and interactive tools for sequence analysis (IMGT/V-QUEST, IMGT/JunctionAnalysis, IMGT/Allele-Align, IMGT/PhyloGene). IMGT data are expertly annotated according to the rules of the IMGT Scientific chart, based on IMGT-ONTOLOGY. IMGT tools are particularly useful for the analysis of the IG and TR repertoires in physiological normal and pathological situations. IMGT has important applications in medical research (autoimmune diseases, AIDS, leukemias, lymphomas, myelomas), biotechnology related to antibody engineering (phage displays, combinatorial libraries) and thera-peutic approaches (graft, immunotherapy). IMGT is freely available at http://imgt.cines.fr.
PMCID: PMC165532  PMID: 12520009
11.  IMGT/LIGM-DB, the IMGT® comprehensive database of immunoglobulin and T cell receptor nucleotide sequences 
Nucleic Acids Research  2005;34(Database issue):D781-D784.
IMGT/LIGM-DB is the IMGT® comprehensive database of immunoglobulin (IG) and T cell receptor (TR) nucleotide sequences from human and other vertebrate species. It was created in 1989 by LIGM, Montpellier, France and is the oldest and the largest database of IMGT®. IMGT/LIGM-DB includes all germline (non-rearranged) and rearranged IG and TR genomic DNA (gDNA) and complementary DNA (cDNA) sequences published in generalist databases. IMGT/LIGM-DB allows searches from the Web interface according to biological and immunogenetic criteria through five distinct modules depending on the user interest. For a given entry, nine types of display are available including the IMGT flat file, the translation of the coding regions and the analysis by the IMGT/V-QUEST tool. IMGT/LIGM-DB distributes expertly annotated sequences. The annotations hugely enhance the quality and the accuracy of the distributed detailed information. They include the sequence identification, the gene and allele classification, the constitutive and specific motif description, the codon and amino acid numbering, and the sequence obtaining information, according to the main concepts of IMGT-ONTOLOGY. They represent the main source of IG and TR gene and allele knowledge stored in IMGT/GENE-DB and in the IMGT reference directory. IMGT/LIGM-DB is freely available at .
doi:10.1093/nar/gkj088
PMCID: PMC1347451  PMID: 16381979
12.  IMGT, the international ImMunoGeneTics database 
Nucleic Acids Research  2000;28(1):219-221.
IMGT, the international ImMunoGeneTics database (http://imgt.cines.fr:8104 ), is a high-quality integrated database specialising in Immunoglobulins (Ig), T cell Receptors (TcR) and Major Histocompatibility Complex (MHC) molecules of all vertebrate species, created in 1989 by Marie-Paule Lefranc, Université Montpellier II, CNRS, Montpellier, France (lefranc@ ligm.igh.cnrs.fr ). At present, IMGT includes two databases: IMGT/LIGM-DB, a comprehensive database of Ig and TcR from human and other vertebrates, with translation for fully annotated sequences, and IMGT/HLA-DB, a database of the human MHC referred to as HLA (Human Leucocyte Antigens). The IMGT server provides a common access to expertized genomic, proteomic, structural and polymorphic data of Ig and TcR molecules of all vertebrates. By its high quality and its easy data distribution, IMGT has important implications in medical research (repertoire in autoimmune diseases, AIDS, leukemias, lymphomas), therapeutic approaches (antibody engineering), genome diversity and genome evolution studies. IMGT is freely available at http://imgt.cines.fr:8104 . The IMGT Index is provided at the IMGT Marie-Paule page (http://imgt.cines.fr:8104/textes/IMGTindex.html ).
PMCID: PMC102442  PMID: 10592230
13.  From IMGT-ONTOLOGY to IMGT/LIGMotif: the IMGT® standardized approach for immunoglobulin and T cell receptor gene identification and description in large genomic sequences 
BMC Bioinformatics  2010;11:223.
Background
The antigen receptors, immunoglobulins (IG) and T cell receptors (TR), are specific molecular components of the adaptive immune response of vertebrates. Their genes are organized in the genome in several loci (7 in humans) that comprise different gene types: variable (V), diversity (D), joining (J) and constant (C) genes. Synthesis of the IG and TR proteins requires rearrangements of V and J, or V, D and J genes at the DNA level, followed by the splicing at the RNA level of the rearranged V-J and V-D-J genes to C genes. Owing to the particularities of IG and TR gene structures related to these molecular mechanisms, conventional bioinformatic software and tools are not adapted to the identification and description of IG and TR genes in large genomic sequences. In order to answer that need, IMGT®, the international ImMunoGeneTics information system®, has developed IMGT/LIGMotif, a tool for IG and TR gene annotation. This tool is based on standardized rules defined in IMGT-ONTOLOGY, the first ontology in immunogenetics and immunoinformatics.
Results
IMGT/LIGMotif currently annotates human and mouse IG and TR loci in large genomic sequences. The annotation includes gene identification and orientation on DNA strand, description of the V, D and J genes by assigning IMGT® labels, gene functionality, and finally, gene delimitation and cluster assembly. IMGT/LIGMotif analyses sequences up to 2.5 megabase pairs and can analyse them in batch files.
Conclusions
IMGT/LIGMotif is currently used by the IMGT® biocurators to annotate, in a first step, IG and TR genomic sequences of human and mouse in new haplotypes and those of closely related species, nonhuman primates and rat, respectively. In a next step, and following enrichment of its reference databases, IMGT/LIGMotif will be used to annotate IG and TR of more distantly related vertebrate species. IMGT/LIGMotif is available at http://www.imgt.org/ligmotif/.
doi:10.1186/1471-2105-11-223
PMCID: PMC2880031  PMID: 20433708
14.  IMGT, the International ImMunoGeneTics database. 
Nucleic Acids Research  1998;26(1):297-303.
IMGT, the international ImMunoGeneTics database, is an integrated database specialising in Immunoglobulins (Ig), T cell Receptors (TcR) and Major Histocompatibility Complex (MHC) of all vertebrate species, created by Marie-Paule Lefranc, CNRS, Montpellier II University, Montpellier, France (lefranc@ligm.crbm.cnrs-mop.fr). IMGT includes three databases: LIGM-DB (for Ig and TcR), MHC/HLA-DB and PRIMER-DB (the last two in development). IMGT comprises expertly annotated sequences and alignment tables. LIGM-DB contains more than 23 000 Immunoglobulin and T cell Receptor sequences from 78 species. MHC/HLA-DB contains Class I and Class II Human Leucocyte Antigen alignment tables. An IMGT tool, DNAPLOT, developed for Ig, TcR and MHC sequence alignments, is also available. IMGT works in close collaboration with the EMBL database. IMGT goals are to establish a common data access to all immunogenetics data, including nucleotide and protein sequences, oligonucleotide primers, gene maps and other genetic data of Ig, TcR and MHC molecules, and to provide a graphical user friendly data access. IMGT has important implications in medical research (repertoire in autoimmune diseases, AIDS, leukemias, lymphomas), therapeutical approaches (antibody engineering), genome diversity and genome evolution studies. IMGT is freely available at http://imgt.cnusc.fr:8104
PMCID: PMC147225  PMID: 9399859
15.  IMGT/V-QUEST: the highly customized and integrated system for IG and TR standardized V-J and V-D-J sequence analysis 
Nucleic Acids Research  2008;36(Web Server issue):W503-W508.
IMGT/V-QUEST is the highly customized and integrated system for the standardized analysis of the immunoglobulin (IG) and T cell receptor (TR) rearranged nucleotide sequences. IMGT/V-QUEST identifies the variable (V), diversity (D) and joining (J) genes and alleles by alignment with the germline IG and TR gene and allele sequences of the IMGT reference directory. New functionalities were added through a complete rewrite in Java. IMGT/V-QUEST analyses batches of sequences (up to 50) in a single run. IMGT/V-QUEST describes the V-REGION mutations and identifies the hot spot positions in the closest germline V gene. IMGT/V-QUEST can detect insertions and deletions in the submitted sequences by reference to the IMGT unique numbering. IMGT/V-QUEST integrates IMGT/JunctionAnalysis for a detailed analysis of the V-J and V-D-J junctions, and IMGT/Automat for a full V-J- and V-D-J-REGION annotation. IMGT/V-QUEST displays, in ‘Detailed view’, the results and alignments for each submitted sequence individually and, in ‘Synthesis view’, the alignments of the sequences that, in a given run, express the same V gene and allele. The ‘Advanced parameters’ allow to modify default parameters used by IMGT/V-QUEST and IMGT/JunctionAnalysis according to the users’ interest. IMGT/V-QUEST is freely available for academic research at http://imgt.cines.fr
doi:10.1093/nar/gkn316
PMCID: PMC2447746  PMID: 18503082
16.  IMGT-ONTOLOGY 2012 
Immunogenetics is the science that studies the genetics of the immune system and immune responses. Owing to the complexity and diversity of the immune repertoire, immunogenetics represents one of the greatest challenges for data interpretation: a large biological expertise, a considerable effort of standardization and the elaboration of an efficient system for the management of the related knowledge were required. IMGT®, the international ImMunoGeneTics information system® (http://www.imgt.org) has reached that goal through the building of a unique ontology, IMGT-ONTOLOGY, which represents the first ontology for the formal representation of knowledge in immunogenetics and immunoinformatics. IMGT-ONTOLOGY manages the immunogenetics knowledge through diverse facets that rely on the seven axioms of the Formal IMGT-ONTOLOGY or IMGT-Kaleidoscope: “IDENTIFICATION,” “DESCRIPTION,” “CLASSIFICATION,” “NUMEROTATION,” “LOCALIZATION,” “ORIENTATION,” and “OBTENTION.” The concepts of identification, description, classification, and numerotation generated from the axioms led to the elaboration of the IMGT® standards that constitute the IMGT Scientific chart: IMGT® standardized keywords (concepts of identification), IMGT® standardized labels (concepts of description), IMGT® standardized gene and allele nomenclature (concepts of classification) and IMGT unique numbering and IMGT Collier de Perles (concepts of numerotation). IMGT-ONTOLOGY has become the global reference in immunogenetics and immunoinformatics for the knowledge representation of immunoglobulins (IG) or antibodies, T cell receptors (TR), and major histocompatibility (MH) proteins of humans and other vertebrates, proteins of the immunoglobulin superfamily (IgSF) and MH superfamily (MhSF), related proteins of the immune system (RPI) of vertebrates and invertebrates, therapeutic monoclonal antibodies (mAbs), fusion proteins for immune applications (FPIA), and composite proteins for clinical applications (CPCA).
doi:10.3389/fgene.2012.00079
PMCID: PMC3358611  PMID: 22654892
IMGT; immunogenetics; immunoinformatics; IMGT-ONTOLOGY; immunoglobulin; antibody; T cell receptor; immune repertoire
17.  IMGT®, the international ImMunoGeneTics information system® 
Nucleic Acids Research  2008;37(Database issue):D1006-D1012.
IMGT®, the international ImMunoGeneTics information system® (http://www.imgt.org), was created in 1989 by Marie-Paule Lefranc, Laboratoire d'ImmunoGénétique Moléculaire LIGM (Université Montpellier 2 and CNRS) at Montpellier, France, in order to standardize and manage the complexity of immunogenetics data. The building of a unique ontology, IMGT-ONTOLOGY, has made IMGT® the global reference in immunogenetics and immunoinformatics. IMGT® is a high-quality integrated knowledge resource specialized in the immunoglobulins or antibodies, T cell receptors, major histocompatibility complex, of human and other vertebrate species, proteins of the IgSF and MhcSF, and related proteins of the immune systems of any species. IMGT® provides a common access to standardized data from genome, proteome, genetics and 3D structures. IMGT® consists of five databases (IMGT/LIGM-DB, IMGT/GENE-DB, IMGT/3Dstructure-DB, etc.), fifteen interactive online tools for sequence, genome and 3D structure analysis, and more than 10 000 HTML pages of synthesis and knowledge. IMGT® is used in medical research (autoimmune diseases, infectious diseases, AIDS, leukemias, lymphomas and myelomas), veterinary research, biotechnology related to antibody engineering (phage displays, combinatorial libraries, chimeric, humanized and human antibodies), diagnostics (clonalities, detection and follow-up of residual diseases) and therapeutical approaches (graft, immunotherapy, vaccinology). IMGT is freely available at http://www.imgt.org.
doi:10.1093/nar/gkn838
PMCID: PMC2686541  PMID: 18978023
18.  An Integrated Tool to Study MHC Region: Accurate SNV Detection and HLA Genes Typing in Human MHC Region Using Targeted High-Throughput Sequencing 
PLoS ONE  2013;8(7):e69388.
The major histocompatibility complex (MHC) is one of the most variable and gene-dense regions of the human genome. Most studies of the MHC, and associated regions, focus on minor variants and HLA typing, many of which have been demonstrated to be associated with human disease susceptibility and metabolic pathways. However, the detection of variants in the MHC region, and diagnostic HLA typing, still lacks a coherent, standardized, cost effective and high coverage protocol of clinical quality and reliability. In this paper, we presented such a method for the accurate detection of minor variants and HLA types in the human MHC region, using high-throughput, high-coverage sequencing of target regions. A probe set was designed to template upon the 8 annotated human MHC haplotypes, and to encompass the 5 megabases (Mb) of the extended MHC region. We deployed our probes upon three, genetically diverse human samples for probe set evaluation, and sequencing data show that ∼97% of the MHC region, and over 99% of the genes in MHC region, are covered with sufficient depth and good evenness. 98% of genotypes called by this capture sequencing prove consistent with established HapMap genotypes. We have concurrently developed a one-step pipeline for calling any HLA type referenced in the IMGT/HLA database from this target capture sequencing data, which shows over 96% typing accuracy when deployed at 4 digital resolution. This cost-effective and highly accurate approach for variant detection and HLA typing in the MHC region may lend further insight into immune-mediated diseases studies, and may find clinical utility in transplantation medicine research. This one-step pipeline is released for general evaluation and use by the scientific community.
doi:10.1371/journal.pone.0069388
PMCID: PMC3722289  PMID: 23894464
19.  IMGT, the international ImMunoGeneTics database. 
Nucleic Acids Research  1999;27(1):209-212.
IMGT, the international ImMunoGeneTics database (http://imgt.cnusc. fr:8104), is a high-quality integrated database specialising in Immunoglobulins (Ig), T cell Receptors (TcR) and Major Histocompatibility Complex (MHC) molecules of all vertebrate species, created in 1989 by Marie-Paule Lefranc, Université Montpellier II, CNRS, Montpellier, France (lefranc@ligm.igh.cnrs.fr). IMGT comprises three databases: LIGM-DB, a comprehensive database of Ig and TcR, MHC/HLA-DB, and PRIMER-DB (the last two in development); a tool, IMGT/DNAPLOT, developed for sequence analysis and alignments; and expertised data based on the IMGT scientific chart, the IMGT repertoire. By its high quality and its easy data distribution, IMGT has important implications in medical research (repertoire in autoimmune diseases, AIDS, leukemias, lymphomas), therapeutic approaches (antibody engineering), genome diversity and genome evolution studies. IMGT is freely available at http://imgt.cnusc. fr:8104
PMCID: PMC148137  PMID: 9847182
20.  IMGT, the international ImMunoGeneTics information system®: a standardized approach for immunogenetics and immunoinformatics 
Immunome Research  2005;1:3.
IMGT, the international ImMunoGeneTics information system®, was created in 1989 by the Laboratoire d'ImmunoGénétique Moléculaire (LIGM) (Université Montpellier II and CNRS) at Montpellier, France. IMGT is a high quality integrated knowledge resource specialized in immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC) of human and other vertebrates, and related proteins of the immune system (RPI) of any species which belong to the immunoglobulin superfamily (IgSF) and to the MHC superfamily (MhcSF). IMGT consists of five databases, ten on-line tools and more than 8,000 HTML pages of Web resources. IMGT provides a common access to standardized data from genome, genetics, proteome and three-dimensional structures. The accuracy and the consistency of IMGT data are based on IMGT-ONTOLOGY, a semantic specification of terms to be used in immunogenetics and immunoinformatics. IMGT-ONTOLOGY comprises six main concepts: IDENTIFICATION, CLASSIFICATION, DESCRIPTION, NUMEROTATION, ORIENTATION and OBTENTION. Based on these concepts, the controlled vocabulary and the annotation rules necessary for the immunogenetics data identification, classification, description and numbering and for the management of IMGT knowledge are defined in the IMGT Scientific chart. IMGT is the international reference in immunogenetics and immunoinformatics for medical research (repertoire analysis of the IG antibody sites and of the TR recognition sites in autoimmune and infectious diseases, AIDS, leukemias, lymphomas, myelomas), veterinary research (IG and TR repertoires in farm and wild life species), genome diversity and genome evolution studies of the adaptive immune responses, biotechnology related to antibody engineering (single chain Fragment variable (scFv), phage displays, combinatorial libraries, chimeric, humanized and human antibodies), diagnostics (detection and follow up of residual diseases) and therapeutical approaches (grafts, immunotherapy, vaccinology). IMGT is freely available at .
doi:10.1186/1745-7580-1-3
PMCID: PMC1312312  PMID: 16305737
IMGT; antibody; immunoglobulin; T cell receptor; superfamily; MHC; HLA; ontology; database; information system; knowledge resource; immunoinformatics; immunogenetics; Collier de Perles; three-dimensional; 3D structure; polymorphism; annotation
21.  Strategies to work with HLA data in human populations for histocompatibility, clinical transplantation, epidemiology and population genetics: HLA-NET methodological recommendations 
HLA-NET (a European COST Action) aims at networking researchers working in bone marrow transplantation, epidemiology and population genetics to improve the molecular characterization of the HLA genetic diversity of human populations, with an expected strong impact on both public health and fundamental research. Such improvements involve finding consensual strategies to characterize human populations and samples and report HLA molecular typings and ambiguities; proposing user-friendly access to databases and computer tools and defining minimal requirements related to ethical aspects. The overall outcome is the provision of population genetic characterizations and comparisons in a standard way by all interested laboratories. This article reports the recommendations of four working groups (WG1-4) of the HLA-NET network at the mid-term of its activities. WG1 (Population definitions and sampling strategies for population genetics’ analyses) recommends avoiding outdated racial classifications and population names (e.g. ‘Caucasian’) and using instead geographic and/or cultural (e.g. linguistic) criteria to describe human populations (e.g. ‘pan-European’). A standard ‘HLA-NET POPULATION DATA QUESTIONNAIRE’ has been finalized and is available for the whole HLA community. WG2 (HLA typing standards for population genetics analyses) recommends retaining maximal information when reporting HLA typing results. Rather than using the National Marrow Donor Program coding system, all ambiguities should be provided by listing all allele pairs required to explain each genotype, according to the formats proposed in ‘HLA-NET GUIDELINES FOR REPORTING HLA TYPINGS’. The group also suggests taking into account a preliminary list of alleles defined by polymorphisms outside the peptide-binding sites that may affect population genetic statistics because of significant frequencies. WG3 (Bioinformatic strategies for HLA population data storage and analysis) recommends the use of programs capable of dealing with ambiguous data, such as the ‘gene[rate]’ computer tools to estimate frequencies, test for Hardy–Weinberg equilibrium and selective neutrality on data containing any number and kind of ambiguities. WG4 (Ethical issues) proposes to adopt thorough general principles for any HLA population study to ensure that it conforms to (inter)national legislation or recommendations/guidelines. All HLA-NET guidelines and tools are available through its website http://hla-net.eu.
doi:10.1111/j.1744-313X.2012.01113.x
PMCID: PMC3533781  PMID: 22533604
22.  IMGT/3Dstructure-DB and IMGT/StructuralQuery, a database and a tool for immunoglobulin, T cell receptor and MHC structural data 
Nucleic Acids Research  2004;32(Database issue):D208-D210.
IMGT/3Dstructure-DB and IMGT/Structural-Query are a novel 3D structure database and a new tool for immunological proteins. They are part of IMGT, the international ImMunoGenetics information system®, a high-quality integrated knowledge resource specializing in immunoglobulins (IG), T cell receptors (TR), major histocompatibility complex (MHC) and related proteins of the immune system (RPI) of human and other vertebrate species, which consists of databases, Web resources and interactive on-line tools. IMGT/3Dstructure-DB data are described according to the IMGT Scientific chart rules based on the IMGT-ONTOLOGY concepts. IMGT/3Dstructure-DB provides IMGT gene and allele identification of IG, TR and MHC proteins with known 3D structures, domain delimitations, amino acid positions according to the IMGT unique numbering and renumbered coordinate flat files. Moreover IMGT/3Dstructure-DB provides 2D graphical representations (or Collier de Perles) and results of contact analysis. The IMGT/StructuralQuery tool allows search of this database based on specific structural characteristics. IMGT/3Dstructure-DB and IMGT/StructuralQuery are freely available at http://imgt.cines.fr.
doi:10.1093/nar/gkh042
PMCID: PMC308776  PMID: 14681396
23.  HLA Alleles Associated with Delayed Progression to AIDS Contribute Strongly to the Initial CD8+ T Cell Response against HIV-1 
PLoS Medicine  2006;3(10):e403.
Background
Very little is known about the immunodominance patterns of HIV-1-specific T cell responses during primary HIV-1 infection and the reasons for human lymphocyte antigen (HLA) modulation of disease progression.
Methods and Findings
In a cohort of 104 individuals with primary HIV-1 infection, we demonstrate that a subset of CD8+ T cell epitopes within HIV-1 are consistently targeted early after infection, while other epitopes subsequently targeted through the same HLA class I alleles are rarely recognized. Certain HLA alleles consistently contributed more than others to the total virus-specific CD8+ T cell response during primary infection, and also reduced the absolute magnitude of responses restricted by other alleles if coexpressed in the same individual, consistent with immunodomination. Furthermore, individual HLA class I alleles that have been associated with slower HIV-1 disease progression contributed strongly to the total HIV-1-specific CD8+ T cell response during primary infection.
Conclusions
These data demonstrate consistent immunodominance patterns of HIV-1-specific CD8+ T cell responses during primary infection and provide a mechanistic explanation for the protective effect of specific HLA class I alleles on HIV-1 disease progression.
A subset of CD8+ T cell epitopes within HIV-1 are consistently targeted early after infection. This could explain some of the protective effect of certain HLA class I alleles on HIV-1 disease progression.
Editors' Summary
Background.
Nearly 15,000 new HIV infections occur each day. There is no cure for HIV, and the treatments currently used to prevent people with HIV from dying are expensive and unavailable to many who need them. There is also no vaccine to prevent HIV. An effective vaccine would somehow induce the immune system to prevent the virus from reaching destructive levels in the body, but how to design such a vaccine is unknown.
In most people infected with HIV, the immune system doesn't keep the AIDS virus in check over the long term. It has been known for a long time, however, that the body somehow brings the virus under control within a few weeks following infection, after which, in the absence of treatment, the amount of virus gradually increases again over time. Exactly why the amount of virus drops after initial infection is not fully understood, but there is good evidence that the white blood cells called CD8 T lymphocytes, which can kill other cells infected with viruses, are at least partially responsible for initially bringing HIV infection under control.
In order for a CD8 T lymphocyte to recognize and kill an infected cell, that cell has to display some part of the infecting virus on its surface. There are many possible fragments of HIV that can activate CD8 T cells, although some of these fragments appear more effective than others at provoking a strong killer response. Also, in order to activate CD8 T cells the viral fragments must bind to and be presented by a particular kind of protein called HLA on the surface of the infected cells. There are hundreds of varieties of HLA in the human population, allowing our immune systems to recognize many parts of many different viruses. (Each person can have up to six different kinds of HLA class I on the surface of his or her cells). A few specific types of HLA have been found to provide some advantage in keeping the AIDS virus under control, possibly because they present fragments of the virus that are particularly good at activating CD8 T cells.
Why Was This Study Done?
The researchers wanted to find out whether specific HLA types and specific protein fragments (peptides) of the AIDS virus are particularly important in helping CD8 T cells control HIV. Specifically, they wanted to find out the very earliest protein fragments recognized, since these might be particularly important in keeping the virus in check. They also wanted to see if these particular HLA-peptide combinations might affect the long-term health of people with HIV infection. Finding specific combinations of peptide and HLA that give rise to strong control of HIV could help in the design of an effective AIDS vaccine.
What Did the Researchers Do and Find?
The researchers studied CD8 T cells in blood samples from 104 people in the early stages of HIV infection. They used DNA analysis to determine which HLA types were present in each participant, and then chose, from among 173 different protein fragments of HIV, the peptides that are known to bind to and be presented by the participant's HLA types. The ability of these peptides to activate the participant's CD8 T cells was measured in the laboratory.
These studies found that for many types of HLA, there were a few specific viral peptides that triggered most of the CD8 T cell activity found in early HIV infection, when the amount of virus in the blood is being lowered by this response. A few types of HLA were found to contribute more strongly than others to CD8 T-cell activity in early HIV infection. These same types of HLA are also found in people who tend to remain healthier for a longer time after becoming infected with HIV.
What Do These Findings Mean?
This study provides evidence that ability of CD8 T cells to keep HIV under control in the first few months following infection depends on a person's HLA composition, and that this early CD8 T cell activity sets the stage for the long-term balance between the body and the virus. Knowing the particular peptide–HLA combinations that dominate the early immune response (when the immune system appears to be bringing the virus under control) might be of use in designing an HIV vaccine. Because this study was done in people already infected with HIV, however, it remains unclear whether a vaccine based on this knowledge would actually prevent new HIV infection or improve health after infection, even in people with “good” HLA types.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030403.
The UCSF Center for HIV Information's HIV InSite includes resources on HIV immunology and vaccine development
The Los Alamos Natural Laboratory HIV Molecular Immunology Database contains information for researchers on HIV peptides, HLA, and CD8 T cell responses
The International AIDS Vaccine Initiative (IAVI) Web site provides policy and scientific information on the global AIDS vaccine effort
The Massachuetts General Hospital Web site contains information about their HIV-1 research programs
doi:10.1371/journal.pmed.0030403
PMCID: PMC1626551  PMID: 17076553
24.  IMGT/V-QUEST, an integrated software program for immunoglobulin and T cell receptor V–J and V–D–J rearrangement analysis 
Nucleic Acids Research  2004;32(Web Server issue):W435-W440.
IMGT/V-QUEST, for ‘V-QUEry and STandardization’, is an integrated software program which analyses the immunoglobulin (IG) and T cell receptor (TR) rearranged nucleotide sequences. The extraordinary diversity of the IG and TR repertoires (1012 antibodies and 1012 TR per individual) results from several mechanisms at the DNA level: the combinatorial diversity of the variable (V), diversity (D) and joining (J) genes, the N-diversity and, for IG, the somatic mutations. IMGT/V-QUEST identifies the V, D and J genes and alleles by alignment with the germline IG and TR gene and allele sequences of the IMGT reference directory. IMGT/V-QUEST delimits the structurally important features, frameworks and complementarity-determining regions (the last of these forming the antigen binding site), on the basis of the IMGT unique numbering. The tool localizes the somatic mutations of the IG rearranged sequences. IMGT/V-QUEST also dynamically displays a graphical two-dimensional representation, or IMGT Collier de Perles, of the IG and TR variable regions. Moreover, IMGT/V-QUEST can interact with IMGT/JunctionAnalysis for the detailed description of the V–J and V–D–J junctions, and with IMGT/PhyloGene for the construction of phylogenetic trees. IMGT/V-QUEST is currently available for human and mouse, and partly for non-human primates, sheep, chondrichthyes and teleostei. IMGT/V-QUEST is freely available at http://imgt.cines.fr.
doi:10.1093/nar/gkh412
PMCID: PMC441550  PMID: 15215425
25.  IMGT/GeneInfo: T cell receptor gamma TRG and delta TRD genes in database give access to all TR potential V(D)J recombinations 
BMC Bioinformatics  2006;7:224.
Background
Adaptative immune repertoire diversity in vertebrate species is generated by recombination of variable (V), diversity (D) and joining (J) genes in the immunoglobulin (IG) loci of B lymphocytes and in the T cell receptor (TR) loci of T lymphocytes. These V-J and V-D-J gene rearrangements at the DNA level involve recombination signal sequences (RSS). Whereas many data exist, they are scattered in non specialized resources with different nomenclatures (eg. flat files) and are difficult to extract.
Description
IMGT/GeneInfo is an online information system that provides, through a user-friendly interface, exhaustive information resulting from the complex mechanisms of T cell receptor V-J and V-D-J recombinations. T cells comprise two populations which express the αβ and γδ TR, respectively. The first version of the system dealt with the Homo sapiens and Mus musculus TRA and TRB loci whose gene rearrangements allow the synthesis of the αβ TR chains. In this paper, we present the second version of IMGT/GeneInfo where we complete the database for the Homo sapiens and Mus musculus TRG and TRD loci along with the introduction of a quality control procedure for existing and new data. We also include new functionalities to the four loci analysis, giving, to date, a very informative tool which allows to work on V(D)J genes of all TR loci in both human and mouse species. IMGT/GeneInfo provides more than 59,000 rearrangement combinations with a full gene description which is freely available at .
Conclusion
IMGT/GeneInfo allows all TR information sequences to be in the same spot, and are now available within two computer-mouse clicks. This is useful for biologists and bioinformaticians for the study of T lymphocyte V(D)J gene rearrangements and their applications in immune response analysis.
doi:10.1186/1471-2105-7-224
PMCID: PMC1482724  PMID: 16640788

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