A mutated HLA-A2 molecule recognized by autologous cytotoxic T lymphocytes on a human renal cell carcinoma.
Many human tumor cells have been shown to express antigens that are recognized by autologous cytotoxic T lymphocytes (CTL) and the molecular nature of a number of melanoma antigens has been defined recently. Here we describe the characterization of an antigen recognized on a renal cell carcinoma by autologous CTL clones. This antigen is encoded by the HLA-A2 gene present in the tumor cells. The sequence of this gene differs from the HLA-A2 sequence found in autologous peripheral blood lymphocytes by a point mutation that results in an arginine to isoleucine exchange at residue 170, which is located on the alpha-helix of the alpha 2 domain. Transfection experiments with the normal and mutated HLA-A2 cDNA demonstrated that this amino acid replacement was responsible for the recognition of the HLA-A2 molecule expressed on the tumor cells. The mutant HLA-A2 gene was also detected in the original tumor tissue from the patient, excluding the possibility that the mutation had appeared in vitro. Thus, HLA class I molecules carrying a tumor-specific mutation can be involved in the recognition of tumor cells by autologous CTL.
Brändle
D
D
Ludwig Institute for Cancer Research, Université Catholique de Louvain, Brussels, Belgium.
Brasseur
F
F
Weynants
P
P
Boon
T
T
Van den Eynde
B
B
D000368:Aged; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002522:Chlorocebus aethiops; D003602:Cytotoxicity, Immunologic; D017931:DNA Primers; D015723:Gene Library; D005805:Genes, MHC Class I; D015789:HLA-A2 Antigen / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000276:immunology*; D008961:Models, Structural; D008969:Molecular Sequence Data; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D017931:DNA Primers; D015789:HLA-A2 Antigen; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha