Major histocompatibility class I (MHC-I) molecules are essential for the control of infections by intracellular pathogens (Klein et al.
). During chaperone-assisted folding in the endoplasmic reticulum (Elliott & Williams, 2005
), each MHC-I molecule binds a peptide from the cytoplasm and transports it to the cell surface, where the peptide–MHC complexes are scrutinized by cytotoxic T lymphocytes (CTL). This sampling of the intracellular protein environment allows CTLs to identify and eliminate infected cells (Townsend & Bodmer, 1989
). In humans, MHC molecules are referred to as human leukocyte antigens (HLAs).
Peptides bind to MHC-I molecules in a special peptide-binding groove, where six binding pockets (A
) determine the specificity of the MHC-I molecule (Garrett et al.
). Most peptides binding to MHC-I molecules consist of 8–11 residues, but binding of peptides up to 14 residues in length has been reported (Probst-Kepper et al.
). MHC-I molecules are highly polymorphic and more than 1000 different variants, each with its own binding specificity, exist in the human population (http://www.anthonynolan.org.uk/HIG/index.html
). Studies of the many MHC-I alleles have allowed a grouping based on peptide-binding preferences and so far 12 different supertypes have been identified (Lund et al.
; Sette & Sidney, 1999
). More than 99% of all humans carry MHC-I molecules belonging to at least one of these supertypes.
HLA-A*1101 is known to be important for the control of infections by many different pathogens including HIV (Culmann et al.
), Epstein–Barr virus (Gavioli et al.
) and hepatitis B virus (HBV; Achour et al.
). It is one of the most common MHC-I alleles and is present in up to 27% of some Asian populations (Bodmer et al.
). Furthermore, it belongs to the A3 supertype, the second most common supertype, found in 44% of the human population (Sette & Sidney, 1999
). Thus, peptides targeting HLA-A*1101 are attractive for inclusion in peptide-based vaccines as they afford broad population coverage and understanding HLA-A*1101 will aid in identifying such peptides. Here, we present the 1.6 Å X-ray structure of a complex of HLA-A*1101 with an HBV peptide homologue.