Faculty Research 1980 - 1989

Title

Expression of histocompatibility antigens H-2K, -D, and -L is reduced in adenovirus-12-transformed mouse cells and is restored by interferon gamma.

Document Type

Article

Publication Date

1985

Keywords

Animal, Antigens-Surface: an, Brain, Cell-Line, Cell-Transformation-Neoplastic, Cytotoxicity-Immunologic, Embryo, H-2-Antigens: ge, Histocompatibility-Antigens: ge, Interferon-Type-II: im, Kidney, Major-Histocompatibility-Complex, Mice, Mice-Inbred-BALB-C, Nucleic-Acid-Hybridization, SUPPORT-U-S-GOVT-P-H-S, T-Lymphocytes: im, Translation-Genetic

JAX Source

Proc Natl Acad Sci U S A 1985 Aug;82(16):5525-9

Grant

CA29797, CA21375, CA32940

Abstract

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.

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