CD8+ T cells from a patient with colon carcinoma, specific for a mutant p21-Ras-derived peptide (Gly13-->Asp), are cytotoxic towards a carcinoma cell line harbouring the same mutation.
Several T lymphocyte clones (TLC), specific for a p21-Ras-derived peptide expressing a Gly13-->Asp mutation and of the CD8+ subtype, were generated from peripheral blood of a colon carcinoma patient. The TLC exerted cytotoxicity against an interferon-gamma (IFN gamma)-pretreated colon carcinoma cell line, HCT116, which harbours the Gly13-->Asp mutation and shares both HLA-A2 and HLA-B12(44) with the patient. This cytotoxic effect could be blocked by a monoclonal antibody (mAb) against CD8 molecules, as well as with a mAb against HLA class I molecules and a polyclonal antiserum against HLA-B12, identifying B12(44) as the antigen-presenting molecule. In growth-inhibition experiments, the growth of both IFN gamma-pretreated and untreated target cells were strongly inhibited by the presence of the CD8+ TLC. Together these data indicate that human cancer cells harbouring a spontaneous ras mutation can process aberrant p21 Ras and express peptide/HLA-class-I complexes on their surface in sufficient density to be recognized by Ras-specific cytotoxic T lymphocytes.
Fossum
B
B
Institute of Transplantation Immunology, National Hospital, University of Oslo, Norway.
Olsen
A C
AC
Thorsby
E
E
Gaudernack
G
G
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D015197:Carcinogenicity Tests; D002999:Clone Cells; D003110:Colonic Neoplasms / Q000235:genetics / Q000276:immunology*; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D005260:Female; D015235:HLA-B Antigens / Q000276:immunology; D006801:Humans; D008875:Middle Aged; D017354:Point Mutation / Q000276:immunology*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D014407:Tumor Cells, Cultured
D015235:HLA-B Antigens; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)