Direct demonstration that cytotoxic T lymphocytes recognize conformational determinants and not primary amino acid sequences.
The bm 1 H-2Kb mutant differs from the parental strain C57BL/6 (B6) only at amino acid (AA) positions 152, 155, and 156 of the H-2K molecule. The H-2Ld molecule is structurally identical with the H-2 Kbm1 molecule from positions 146-162, thus including all three AA substitutions in Kbm1. In direct lysis and monolayer adsorption studies, B6 anti-bml cytotoxic T lymphocytes (CTL) were shown to include at least five distinct CTL subsets of the following specificities. (a) Uniquely reactive with Kbm1; (b) cross-reactive with Kk; (c) cross-reactive with Dk; (d) cross-reactive with H-2d minus Ld, and (e) cross-reactive with Ld. If B6 anti-bm1 CTL were directed against the primary AA-sequence difference, then all five subsets are expected to react with Ld. However, four out of five CTL subsets including a major population uniquely directed against Kbm1 failed to react with Ld. These findings strongly strengthen the notion that CTL recognize conformational determinants and not primary AA sequences.
D000595:Amino Acid Sequence; D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D000939:Epitopes / Q000276:immunology*; D006183:H-2 Antigens / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008817:Mice, Mutant Strains; D008968:Molecular Conformation; D009154:Mutation; D013329:Structure-Activity Relationship; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D006183:H-2 Antigens; C032876:H-2Kb protein, mouse