Major Histocompatibility Complex: Interaction with Peptides

Abstract

Abstract T‐cell‐specific immunity functions in a major histocompatibility complex (MHC)‐dependent manner. MHC molecules present antigenic peptides on the surface of cells to be recognised by specific T‐cells. MHC class I and class II molecules possess highly similar structural features used to load peptides. Specifically, both contain peptide‐binding grooves formed by two α‐helices and eight β‐strands. In the peptide‐binding groove, specific amino acids compose pockets that accommodate the corresponding side chains of the anchor residues of the presented peptides. Peptide‐binding preferences exist among different alleles of both of MHC I and MHC II molecules, which are mainly dependent on amino acid polymorphisms in the peptide‐binding grooves of MHC chains. Aside from the common binding of peptides to MHC molecules, the currently determined structures of post‐translationally modified peptides to MHC molecules demonstrate that the modified groups have important roles in the peptide–MHC interaction. The illumination of the binding features of peptides to MHC molecules has aided our understanding of T‐cell‐specific immunity and the development of T‐cell epitope‐related vaccines. Key Concepts: MHC I and class II molecules fold into a highly similar conformations featuring a peptide‐binding groove to present T‐cell epitopes. Peptide‐binding grooves of MHC I molecules are composed of two α‐helices and eight β‐strands formed by one heavy chain, while MHC II uses two domains from different chains to construct the peptide‐binding groove. Peptides bind to MHC molecules through primary and secondary anchor residues protruding into the pockets in the peptide‐binding grooves. Peptide preferences are dependent on the amino acids polymorphisms comprising the anchor pockets, which are related to the various alleles of MHC. The conformations of peptides presented by MHC I molecules are length‐dependant. The modified groups of post‐translationally modified peptides have important roles in the peptide–MHC interaction. MHC is called HLA, human leucocyte antigen, in human; H‐2 in mice.