Structure of HLA-B27-specific T cell epitopes. Antigen presentation in B*2703 is limited mostly to a subset of the antigenic determinants on B*2705.
The 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 through the peptide binding site.
Villadangos
J A
JA
Centro de Biología Molecular Severo Ochoa, Universidad Autónoma de Madrid, Cantoblanco, Spain.
Galocha
B
B
García-Hoyo
R
R
López
D
D
García
F
F
López de Castro
J A
JA
D000938:Antigen-Presenting Cells / Q000276:immunology*; D003429:Cross Reactions; D003602:Cytotoxicity, Immunologic; D000939:Epitopes; D015796:HLA-B27 Antigen / Q000276:immunology*; D006801:Humans; D016297:Mutagenesis, Site-Directed; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D015796:HLA-B27 Antigen