In this study the immunogenic tryptic fragment from a horse cytochrome c (cyt c) digest recognized by cytotoxic T lymphocytes (CTL), induced by in vitro peptide stimulation from C57BL/6 (B6) and mutant B6.C‐H‐2bm1 (bm1) mice is identified. An identical sequence, p40—53, is recognized by CTL from both B6 and bm1 mice. In addition, both B6 and bm1 cloned CTL lines display unusual major histocompatibility complex (MHC) class I‐restricted recognition of this peptide in that they respond to it in the context of H‐2Kb, H‐2Db, and H‐2Kbm1 class I molecules, although the sequence lacks the usual structural Kb and Db peptide‐binding motifs. Truncated analogues which resemble the lengths of naturally processed MHC class I‐presented peptides, confer reactivity for B6 and bm1 CTL against EL4 (H‐2b) targets as well as the L cell transfectants, L + Kb, L + Db, and L + Kbm1. The antigenic peptide with the greatest potency is p41—49, which appears to be generated by angiotensin converting enzyme cleavage of the full‐length p40—53 tryptic peptide. The minimum antigenic peptide recognized by both B6 and bm1 CTL, and which targets lysis on each of the transfectants, is the hexamer p43—48 peptide from horse cyt c. Residues Pro44 and Thr47, which occupy polymorphic positions with respect to other species‐variant cyt c molecules, influence recognition of these peptides differently for the B6 and bm1 CTL. The ability of H‐2Kb, H‐2Db, and mutant H‐2Kbm1 class I molecules to present the same peptide to a single cloned CTL is discussed in the context of current knowledge of peptide anchor residues and side chain‐specific binding pockets in the MHC class I peptide‐binding site.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy