Structure of HLA‐B27‐specific T cell epitopes. Antigen presentation in B2703 is limited mostly to a subset of the antigenic determinants on B2705

摘要

AbstractThe structure of HLA‐B27‐specific epitopes recognized by anti‐B*2705 and anti‐B*2703 cytotoxic T lymphocytes (CTL) from three unrelated donors was examined with site‐specific mutants at various side‐chain pockets in the antigen‐binding site. The effect of any given mutation on allorecognition correlated strongly with its predictable effect on peptide binding. Acidic charges in the C/F pocket of HLA‐B27, which binds C‐terminal peptide residues, strongly modulated allorecognition. Anti‐B*2705 CTL from different donors were differently affected by some mutations, indicating individual differences in the structure of epitopes recognized by alloreactive CTL from each donor. Most anti‐B*2703 CTL recognized a subset of epitopes that were also present on B*2705, but differed from the bulk of allospecific epitopes on this subtype in their smaller dependence on pocket A structure, where the difference between these subtypes is located, and in their greater dependence on Glu45, in the B pocket. The structure of the very few epitopes on B*2703 not shared by B*2705 was quite different from that of the much more predominant cross‐reactive epitopes. The results strongly suggest that B*2703 is antigenically defective as compared with B*2705 and that this is due to the fact that the repertoire of peptides presented by B*2703 consists mainly of a subset of the B*2705‐bound peptides which do not critically require the canonic binding of the peptidic N‐terminus to a B*2705‐like A pocket, because they are sufficiently stabilized by other contacts thr