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Although Major Histocompatibility Complex (MHC) restricted antigen recognition was first described in the early years of the 1970s (Klein, 1986), it was not until 1987 that it became clear what the precise biochemical nature of this restriction was. Detailed X-ray crystallographic data of the human class I heterodimer (HLA-A2) molecule revealed the presence of a peptide inside a groove formed by alpha helices and antiparallel beta-strands of the class I MHC molecule (Bjorkman et al., 1987; Saper et al., 1991). The peptide/MHC molecule complex forms the ligand for the T cell receptor (TCR), and in this way dictates the restricted recognition of non-self peptides and self MHC molecules (Germain & Margulies, 1993). Similarly, the human MHC class II (HLA-DR1) molecules were also found to be comparably structured to MHC class I molecules (Brown et al., 1993). However, class I molecules use the a1 and a2 domains to shape the peptide binding region (PBR), whereas class II molecules utilise the a1 and â1 domains. Class I molecules can be divided into classical (class I-a) and non-classical (class I-b). Both are non-covalently associated with â2-microglobulin. The di#erences between these two types of class I molecules is that, in general, class I-a molecules are highly polymorphic, but encoded only by a few loci, whereas class I-b are oligomorphic, but are sometimes encoded by numerous loci. However, the similarity between the two types is the fact that they both are able to bind and present peptides, with some exceptions such as the FcRn molecule (Shawar et al., 1994). The three-dimensional structure of class I molecules showed that both ends of the groove are occluded, which restricts the length of the peptide that can be bound in the groove to 8–12 amino acids. The peptide can interact with six binding pockets, of which two serve as conserved anchors to bind the Nand C-terminus of the peptide. The other |
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