Structural requirements for the interaction between class II MHC molecules and peptide antigens.
Previous work from our and other laboratories indicates that T cells recognize a complex between the MHC restriction element and peptide antigen fragments. This paper reviews the structural characteristics of the formation of such a complex. By analyzing in detail the interactions between purified IA(d) and IE(d) molecules and their peptide ligands, we found that some structural characteristics apply to both antigen-MHC interactions. In particular, we found: 1) each MHC molecule is capable of binding many unrelated peptides through the same peptide-binding site; 2) despite this permissiveness of binding, it is possible to define certain structural features of peptides that are associated with the capacity to bind to a particular MHC specificity (IA(d) or IE(d)); 3) IA(d) and IE(d) molecules recognize different and independent structures on the antigen molecule; 4) only about 10% of the single amino acid substitutions tested on two IA(d)- and IE(d)-binding peptides had significant effect on their MHC-binding capacities, while over 80% of these substitutions significantly impaired T cell recognition of the Ia-peptide complex; 5) based on the segregation between residues that are crucial for T cell activation and Ia binding, the easiest model for the antigen-Ia-T-cell-receptor complex pictures the antigen molecule sandwiched in a planar conformation between the MHC and the T cell.
Cytel, La Jolla, Calif.
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D000595:Amino Acid Sequence; D000818:Animals; D000941:Antigens / Q000235:genetics*; D000949:Histocompatibility Antigens Class II / Q000235:genetics*; D008969:Molecular Sequence Data; D010455:Peptides / Q000276:immunology*; D011485:Protein Binding
D000941:Antigens; D000949:Histocompatibility Antigens Class II; D010455:Peptides