Chemistry of peptides associated with MHC class I and class II molecules

Recent developments have led to a clearer understanding of the association between peptides and MHC molecules. It is now clear that the peptides presented by MHC class I or class II molecules follow stringent rules that are different for each allelic product. The allele-specific interaction usually involves sequence of nine amino acids spanning the MHC groove. For class I molecules, the entire peptide ligand is involved in allele-specific interaction with MHC but for class II, the peptides are longer and the nine amino acid sequence is roughly central to the peptide. Allele-specific interactions are brought about by anchoring peptide side chains in complementary pockets in the MHC groove. The sum of allele-specific peptide—MHC interaction requirements can be described as a motif, characterized by number, spacing and specificities of anchors, as well as the more degenerate preferences at non-anchor positions within the nonamer stretches. Such information is useful for T-cell epitope predictions.