Expression of histocompatibility antigens H-2K, -D, and -L is reduced in adenovirus-12-transformed mouse cells and is restored by interferon gamma.
Primary mouse cells transformed by adenovirus type 12 (Ad12) expressed negligible amounts of class I antigens H-2K, -D, and -L on the cell surface and were capable of forming tumors in syngeneic animals, whereas cells transformed by Ad5 continued to express class I antigens and were nontumorigenic. Cells from a tumor, generated by injection of Ad12-transformed mouse cells into a syngeneic mouse, also expressed low levels of H-2 antigens, indicating that this phenotype is maintained in vivo. In all Ad12-transformed cells, synthesis of the H-2 heavy chain was not detected whereas the beta 2-microglobulin light chain was synthesized. Furthermore, the level of cytoplasmic H-2 mRNA in the Ad12 lines was greatly reduced. Reduction of H-2 expression is instructed solely by the transforming region of the viral genome, since this repression occurred in cells transformed by a DNA fragment containing only Ad12 E1A and E1B genes. Addition of recombinant murine interferon gamma strongly stimulated expression of class I antigens in the Ad12 transformants as well as in cells from the Ad12 tumor. This result indicates that Ad12 does not preferentially transform cells that are deficient for class I genes and that Ad12 does not mutate the class I genes in cells it transforms. The correlation between tumorigenicity and loss of H-2 expression in Ad12-transformed cells is discussed.
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D000954:Antigens, Surface / Q000032:analysis; D001921:Brain; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D003602:Cytotoxicity, Immunologic; D004622:Embryo, Mammalian; D006183:H-2 Antigens / Q000235:genetics; D064532:Histocompatibility Antigen H-2D; D006649:Histocompatibility Antigens / Q000235:genetics*; D007371:Interferon-gamma / Q000276:immunology*; D007668:Kidney; D008285:Major Histocompatibility Complex; D051379:Mice; D008807:Mice, Inbred BALB C; D009693:Nucleic Acid Hybridization; D014176:Protein Biosynthesis; D013601:T-Lymphocytes / Q000276:immunology
D000954:Antigens, Surface; D006183:H-2 Antigens; C024755:H-2K(K) antigen; D064532:Histocompatibility Antigen H-2D; D006649:Histocompatibility Antigens; D007371:Interferon-gamma