FIGURE 23-24 Peptide binding and MHC restriction. (a) Peptides that bind to class I molecules are on average 8–10 residues in length, require proper accommodation of the termini, and include two or three residues that are conserved (anchor residues). Positions in class I molecules that distinguish one allele from another (polymorphic residues) occur in and around the peptide-binding cleft. The polymorphic residues in the MHC affect both the specificity of peptide binding and interactions with T-cell receptors. Successful “recognition” of an antigenic peptide–MHC complex by a T-cell receptor requires a good fit among the receptor, peptide, and MHC molecule. (b) Steric clash and a lack of complementarity between anchor residues and the MHC molecule prevent proper binding. T-cell receptors are thus restricted to binding specific peptide-MHC complexes.