Unconventional cytotoxic T lymphocyte recognition of synthetic peptides corresponding to residues 1-23 of Ras protein.
A peptide corresponding to amino acids 1 through 23 of Ras protein containing a mutation at position 12 was used to induce cytotoxic T lymphocytes (CTL) in mice. Although the CTL were CD8+ and expressed alpha, beta T cell antigen receptors (TCR), their major histocompatibility complex (MHC)-restriction was unconventional. They recognized peptide-treated murine cells of different H-2 haplotypes, but not MHC class I-negative cells. Human HLA class I molecules did not present Ras peptides and hybrid human/mouse MHC molecules revealed that all three extracellular domains alpha 1, alpha 2 and alpha 3 were required for recognition by peptide-specific CTL. Shortening the 23-mer peptide by 5 residues at either the amino or carboxy terminus resulted in loss of CTL recognition. This demonstrates an unusual form of antigen recognition by mouse CTL in which peptide presentation requires murine H-2 class I molecules but is not class I allele restricted, and the peptides recognized are much larger than peptides in conventional class I-restricted responses.
Yin
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Imperial Cancer Research Fund, Tumour Immunology Unit, University College London Medical School, Great Britain.
Thomas
C
C
Hsuan
J J
JJ
Stauss
H J
HJ
D000595:Amino Acid Sequence; D000818:Animals; D003601:Cytotoxicity Tests, Immunologic; D006801:Humans; D008285:Major Histocompatibility Complex / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000276:immunology*; D011994:Recombinant Proteins / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D010446:Peptide Fragments; D011994:Recombinant Proteins; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)