0000000000025296
AUTHOR
E De Plaen
Identification of Point Mutations in Genes Coding for tum-Antigens. A Step Towards the Understanding of Mouse and Human Tumor-Specific Transplantation Antigens?
Most experimental tumors induced with chemical carcinogens or UV radiation express individually specific transplantation antigens that elicit a T cell-mediated immune rejection in the syngeneic animals (Prehn and Main 1957; Klein et al. 1960; Kripke 1981; Uyttenhove et al. 1983). The characterization of these transplantation antigens has proved very difficult and several different approaches have been followed. One involves the search for specific antibodies to isolate the antigen by immunoprecipitation. Unfortunately, tumors seldom elicit antibodies directed against their specific transplantation antigens. One notable exception is UV-induced tumor 1591, and the molecules that were isolated…
A p16INK4a-insensitive CDK4 mutant targeted by cytolytic T lymphocytes in a human melanoma.
A mutated cyclin-dependent kinase 4 (CDK4) was identified as a tumor-specific antigen recognized by HLA-A2. 1-restricted autologous cytolytic T lymphocytes (CTLs) in a human melanoma. The mutated CDK4 allele was present in autologous cultured melanoma cells and metastasis tissue, but not in the patient's lymphocytes. The mutation, an arginine-to-cysteine exchange at residue 24, was part of the CDK4 peptide recognized by CTLs and prevented binding of the CDK4 inhibitor p16INK4a, but not of p21 or of p27KIP1. The same mutation was found in one additional melanoma among 28 melanomas analyzed. These results suggest that mutation of CDK4 can create a tumor-specific antigen and can disrupt the ce…
A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma.
Many human melanoma tumors express antigens that are recognized in vitro by cytolytic T lymphocytes (CTLs) derived from the tumor-bearing patient. A gene was identified that directed the expression of antigen MZ2-E on a human melanoma cell line. This gene shows no similarity to known sequences and belongs to a family of at least three genes. It is expressed by the original melanoma cells, other melanoma cell lines, and by some tumor cells of other histological types. No expression was observed in a panel of normal tissues. Antigen MZ2-E appears to be presented by HLA-A1; anti-MZ2-E CTLs of the original patient recognized two melanoma cell lines of other HLA-A1 patients that expressed the ge…