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J Exp Med. 1987 November 1; 166(5): 1548–1566.
PMCID: PMC2189669

Differential usage of three exons generates at least five different mRNAs encoding human leukocyte common antigens


Leukocyte common antigens (LCAs, also known as T200 and CD 45) are integral membrane proteins expressed exclusively on hematopoietic cells. These molecules exhibit varying molecular masses and epitopes when expressed in different cell types. To determine the genetic bases for the generation of this diversity, three classes of human LCA cDNA clones that are different near their 5' ends have been isolated. These differences arose as a result of differential usage of three exons as determined from an analysis of a genomic DNA clone. Furthermore, Northern blot analysis with LCA exon-specific probes demonstrates the existence of at least two more LCA mRNA forms that are generated by differential splicing. A comparison of the human and mouse LCA protein sequences revealed a marked difference only in the extracellular domain.

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Selected References

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  • Reinherz EL, Schlossman SF. The differentiation and function of human T lymphocytes. Cell. 1980 Apr;19(4):821–827. [PubMed]
  • Morimoto C, Letvin NL, Distaso JA, Aldrich WR, Schlossman SF. The isolation and characterization of the human suppressor inducer T cell subset. J Immunol. 1985 Mar;134(3):1508–1515. [PubMed]
  • Takeuchi T, Rudd CE, Schlossman SF, Morimoto C. Induction of suppression following autologous mixed lymphocyte reaction; role of a novel 2H4 antigen. Eur J Immunol. 1987 Jan;17(1):97–103. [PubMed]
  • Omary MB, Trowbridge IS, Battifora HA. Human homologue of murine T200 glycoprotein. J Exp Med. 1980 Oct 1;152(4):842–852. [PMC free article] [PubMed]
  • Dalchau R, Fabre JW. Identification with a monoclonal antibody of a predominantly B lymphocyte-specific determinant of the human leukocyte common antigen. Evidence for structural and possible functional diversity of the human leukocyte common molecule. J Exp Med. 1981 Apr 1;153(4):753–765. [PMC free article] [PubMed]
  • Berger AE, Davis JE, Cresswell P. A human leukocyte antigen identified by a monoclonal antibody. Hum Immunol. 1981 Nov;3(3):231–245. [PubMed]
  • Ledbetter JA, Rose LM, Spooner CE, Beatty PG, Martin PJ, Clark EA. Antibodies to common leukocyte antigen p220 influence human T cell proliferation by modifying IL 2 receptor expression. J Immunol. 1985 Sep;135(3):1819–1825. [PubMed]
  • Nieminen P, Saksela E. NK-9, a distinct sialylated antigen of the T200 family. Eur J Immunol. 1986 May;16(5):513–518. [PubMed]
  • Tung JS, Scheid MP, Pierotti MA, Hämmerling U, Boyse EA. Structural features and selective expression of three Ly-5+ cell-surface molecules. Immunogenetics. 1981;14(1-2):101–106. [PubMed]
  • Sarmiento M, Loken MR, Trowbridge IS, Coffman RL, Fitch FW. High molecular weight lymphocyte surface proteins are structurally related and are expressed on different cell populations at different times during lymphocyte maturation and differentiation. J Immunol. 1982 Apr;128(4):1676–1684. [PubMed]
  • Lefrançois L, Bevan MJ. Novel antigenic determinants of the T200 glycoprotein expressed preferentially by activated cytotoxic T lymphocytes. J Immunol. 1985 Jul;135(1):374–383. [PubMed]
  • Woollett GR, Barclay AN, Puklavec M, Williams AF. Molecular and antigenic heterogeneity of the rat leukocyte-common antigen from thymocytes and T and B lymphocytes. Eur J Immunol. 1985 Feb;15(2):168–173. [PubMed]
  • Spickett GP, Brandon MR, Mason DW, Williams AF, Woollett GR. MRC OX-22, a monoclonal antibody that labels a new subset of T lymphocytes and reacts with the high molecular weight form of the leukocyte-common antigen. J Exp Med. 1983 Sep 1;158(3):795–810. [PMC free article] [PubMed]
  • Houssaint E, Tobin S, Cihak J, Lösch U. A chicken leukocyte common antigen: biochemical characterization and ontogenetic study. Eur J Immunol. 1987 Feb;17(2):287–290. [PubMed]
  • Thomas ML, Barclay AN, Gagnon J, Williams AF. Evidence from cDNA clones that the rat leukocyte-common antigen (T200) spans the lipid bilayer and contains a cytoplasmic domain of 80,000 Mr. Cell. 1985 May;41(1):83–93. [PubMed]
  • Saga Y, Tung JS, Shen FW, Boyse EA. Sequences of Ly-5 cDNA: isoform-related diversity of Ly-5 mRNA. Proc Natl Acad Sci U S A. 1986 Sep;83(18):6940–6944. [PubMed]
  • Morishima Y, Ogata S, Collins NH, Dupont B, Lloyd KO. Carbohydrate differences in human high molecular weight antigens of B- and T-cell lines. Immunogenetics. 1982;15(5):529–535. [PubMed]
  • Childs RA, Dalchau R, Scudder P, Hounsell EF, Fabre JW, Feizi T. Evidence for the occurrence of O-glycosidically linked oligosaccharides of poly-N-acetyllactosamine type on the human leucocyte common antigen. Biochem Biophys Res Commun. 1983 Jan 27;110(2):424–431. [PubMed]
  • Lefrancois L, Thomas ML, Bevan MJ, Trowbridge IS. Different classes of T lymphocytes have different mRNAs for the leukocyte-common antigen, T200. J Exp Med. 1986 May 1;163(5):1337–1342. [PMC free article] [PubMed]
  • Raschke WC. Cloned murine T200 (Ly-5) cDNA reveals multiple transcripts within B- and T-lymphocyte lineages. Proc Natl Acad Sci U S A. 1987 Jan;84(1):161–165. [PubMed]
  • Weis JJ, Fearon DT, Klickstein LB, Wong WW, Richards SA, de Bruyn Kops A, Smith JA, Weis JH. Identification of a partial cDNA clone for the C3d/Epstein-Barr virus receptor of human B lymphocytes: homology with the receptor for fragments C3b and C4b of the third and fourth components of complement. Proc Natl Acad Sci U S A. 1986 Aug;83(15):5639–5643. [PubMed]
  • Lawn RM, Fritsch EF, Parker RC, Blake G, Maniatis T. The isolation and characterization of linked delta- and beta-globin genes from a cloned library of human DNA. Cell. 1978 Dec;15(4):1157–1174. [PubMed]
  • Benton WD, Davis RW. Screening lambdagt recombinant clones by hybridization to single plaques in situ. Science. 1977 Apr 8;196(4286):180–182. [PubMed]
  • Rigby PW, Dieckmann M, Rhodes C, Berg P. Labeling deoxyribonucleic acid to high specific activity in vitro by nick translation with DNA polymerase I. J Mol Biol. 1977 Jun 15;113(1):237–251. [PubMed]
  • Wahl GM, Stern M, Stark GR. Efficient transfer of large DNA fragments from agarose gels to diazobenzyloxymethyl-paper and rapid hybridization by using dextran sulfate. Proc Natl Acad Sci U S A. 1979 Aug;76(8):3683–3687. [PubMed]
  • Southern EM. Detection of specific sequences among DNA fragments separated by gel electrophoresis. J Mol Biol. 1975 Nov 5;98(3):503–517. [PubMed]
  • Melton DA, Krieg PA, Rebagliati MR, Maniatis T, Zinn K, Green MR. Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. Nucleic Acids Res. 1984 Sep 25;12(18):7035–7056. [PMC free article] [PubMed]
  • Maxam AM, Gilbert W. Sequencing end-labeled DNA with base-specific chemical cleavages. Methods Enzymol. 1980;65(1):499–560. [PubMed]
  • Thomas PS. Hybridization of denatured RNA transferred or dotted nitrocellulose paper. Methods Enzymol. 1983;100:255–266. [PubMed]
  • Proudfoot NJ, Brownlee GG. 3' non-coding region sequences in eukaryotic messenger RNA. Nature. 1976 Sep 16;263(5574):211–214. [PubMed]
  • Kozak M. Point mutations define a sequence flanking the AUG initiator codon that modulates translation by eukaryotic ribosomes. Cell. 1986 Jan 31;44(2):283–292. [PubMed]
  • Kyte J, Doolittle RF. A simple method for displaying the hydropathic character of a protein. J Mol Biol. 1982 May 5;157(1):105–132. [PubMed]
  • von Heijne G. A new method for predicting signal sequence cleavage sites. Nucleic Acids Res. 1986 Jun 11;14(11):4683–4690. [PMC free article] [PubMed]
  • Mount SM. A catalogue of splice junction sequences. Nucleic Acids Res. 1982 Jan 22;10(2):459–472. [PMC free article] [PubMed]
  • Leff SE, Rosenfeld MG, Evans RM. Complex transcriptional units: diversity in gene expression by alternative RNA processing. Annu Rev Biochem. 1986;55:1091–1117. [PubMed]
  • Breitbart RE, Nguyen HT, Medford RM, Destree AT, Mahdavi V, Nadal-Ginard B. Intricate combinatorial patterns of exon splicing generate multiple regulated troponin T isoforms from a single gene. Cell. 1985 May;41(1):67–82. [PubMed]
  • Hemperly JJ, Murray BA, Edelman GM, Cunningham BA. Sequence of a cDNA clone encoding the polysialic acid-rich and cytoplasmic domains of the neural cell adhesion molecule N-CAM. Proc Natl Acad Sci U S A. 1986 May;83(9):3037–3041. [PubMed]
  • Zamoyska R, Vollmer AC, Sizer KC, Liaw CW, Parnes JR. Two Lyt-2 polypeptides arise from a single gene by alternative splicing patterns of mRNA. Cell. 1985 Nov;43(1):153–163. [PubMed]
  • Nakauchi H, Nolan GP, Hsu C, Huang HS, Kavathas P, Herzenberg LA. Molecular cloning of Lyt-2, a membrane glycoprotein marking a subset of mouse T lymphocytes: molecular homology to its human counterpart, Leu-2/T8, and to immunoglobulin variable regions. Proc Natl Acad Sci U S A. 1985 Aug;82(15):5126–5130. [PubMed]
  • Littman DR. The structure of the CD4 and CD8 genes. Annu Rev Immunol. 1987;5:561–584. [PubMed]
  • Ullrich A, Coussens L, Hayflick JS, Dull TJ, Gray A, Tam AW, Lee J, Yarden Y, Libermann TA, Schlessinger J, et al. Human epidermal growth factor receptor cDNA sequence and aberrant expression of the amplified gene in A431 epidermoid carcinoma cells. Nature. 309(5967):418–425. [PubMed]
  • Yarden Y, Escobedo JA, Kuang WJ, Yang-Feng TL, Daniel TO, Tremble PM, Chen EY, Ando ME, Harkins RN, Francke U, et al. Structure of the receptor for platelet-derived growth factor helps define a family of closely related growth factor receptors. Nature. 1986 Sep 18;323(6085):226–232. [PubMed]
  • Coussens L, Van Beveren C, Smith D, Chen E, Mitchell RL, Isacke CM, Verma IM, Ullrich A. Structural alteration of viral homologue of receptor proto-oncogene fms at carboxyl terminus. Nature. 1986 Mar 20;320(6059):277–280. [PubMed]
  • Bargmann CI, Hung MC, Weinberg RA. The neu oncogene encodes an epidermal growth factor receptor-related protein. Nature. 1986 Jan 16;319(6050):226–230. [PubMed]
  • Yamamoto T, Ikawa S, Akiyama T, Semba K, Nomura N, Miyajima N, Saito T, Toyoshima K. Similarity of protein encoded by the human c-erb-B-2 gene to epidermal growth factor receptor. Nature. 1986 Jan 16;319(6050):230–234. [PubMed]
  • Omary MB, Trowbridge IS. Disposition of T200 glycoprotein in the plasma membrane of a murine lymphoma cell line. J Biol Chem. 1980 Feb 25;255(4):1662–1669. [PubMed]
  • Shackelford DA, Trowbridge IS. Identification of lymphocyte integral membrane proteins as substrates for protein kinase C. Phosphorylation of the interleukin-2 receptor, class I HLA antigens, and T200 glycoprotein. J Biol Chem. 1986 Jun 25;261(18):8334–8341. [PubMed]
  • Ralph SJ, Thomas ML, Morton CC, Trowbridge IS. Structural variants of human T200 glycoprotein (leukocyte-common antigen). EMBO J. 1987 May;6(5):1251–1257. [PubMed]
  • Barclay AN, Jackson DI, Willis AC, Williams AF. Lymphocyte specific heterogeneity in the rat leucocyte common antigen (T200) is due to differences in polypeptide sequences near the NH2-terminus. EMBO J. 1987 May;6(5):1259–1264. [PubMed]

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