Mechanism of induction of class I major histocompatibility antigen expression by murine leukemia virus.
Alterations in expression of major histocompatibility complex (MHC) antigens on tumor cells clearly correlate with the tumorgenicity and metastatic potential of those cells. These changes in the biological behavior of the tumor cells are presumably secondary to resulting changes in their susceptibility to immune recognition and destruction. Murine leukemia viruses (MuLV) exert regulatory effects on class I genes of the MHC locus. MuLV infection results in substantial increases in cell surface expression of all three class I MHC antigens. These viral effects on MHC antigen expression profoundly influence immune-mediated interaction with the infected cells, as assessed by cytotoxic T lymphocyte recognition and killing. Control of class I MHC and beta-2 microglobulin genes by MuLV takes place via a trans-acting molecular mechanism. MuLV controls expression of widely separated endogenous cellular MHC genes, transfected xenogeneic class I MHC genes, and unintegrated chimeric genes consisting of fragments of class I MHC genes linked to a bacterial reporter gene. These findings indicate that MuLV exerts its effects on MHC expression via a trans mechanism. The MuLV-responsive sequences on the MHC genes appear to lie within 1.2 kilobases upstream of the initiation codon for those genes.
Faller
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DV
Division of Pediatric Oncology, Dana Farber Cancer Institute, Boston, Massachusetts.
Wilson
L D
LD
Flyer
D C
DC
D000818:Animals; D000911:Antibodies, Monoclonal; D002478:Cells, Cultured; D002860:Chromium Radioisotopes; D004926:Escherichia coli / Q000235:genetics; D005347:Fibroblasts / Q000382:microbiology; D005455:Fluorescent Antibody Technique; D005798:Genes, Bacterial; D005805:Genes, MHC Class I; D006183:H-2 Antigens / Q000235:genetics*; D007157:Immunologic Surveillance; D051379:Mice; D008979:Moloney murine leukemia virus / Q000235:genetics*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014162:Transfection
D000911:Antibodies, Monoclonal; D002860:Chromium Radioisotopes; D006183:H-2 Antigens