Retrovirus-induced changes in major histocompatibility complex antigen expression influence susceptibility to lysis by cytotoxic T lymphocytes.
Retrovirus infection of murine fibroblasts was found to alter the expression of major histocompatibility complex (MHC) antigens. Fibroblasts infected with Moloney murine leukemia virus (M-MuLV) exhibited up to a 10-fold increase in cell surface expression of all three class I MHC antigens. Increases in MHC expression resulted in the increased susceptibility of M-MuLV-infected cells to lysis by allospecific cytotoxic T lymphocytes (CTL). M-MuLV appears to exert its effect at the genomic level, because mRNA specific for class I antigens, as well as beta 2-microglobulin, show a fourfold increase. Fibroblasts infected with the Moloney sarcoma virus (MSV):M-MuLV complex show no increase in MHC antigen expression or class I mRNA synthesis, suggesting that co-infection with MSV inhibits M-MuLV enhancement of MHC gene expression. Quantitative differences in class I antigen expression on virus-infected cells were also found to influence the susceptibility of infected cells to lysis by H-2-restricted, virus-specific CTL. Differential lysis of infected cells expressing varied levels of class I antigens by M-MuLV-specific bulk CTL populations and CTL clones suggests that individual clones may have different quantitative requirements for class I antigen expression. The MSV inhibition of MHC expression could be reversed by interferon-gamma. Treatment of MSV:M-MuLV-infected fibroblasts with interferon-gamma increased their susceptibility to lysis by both allogeneic and syngeneic CTL. The data suggest that interferon-gamma may function in the host's immune response to viral infections by enhancing MHC antigen expression, thereby increasing the susceptibility of virus-infected cells to lysis by H-2-restricted, virus-specific CTL.
D C
DC
Flyer
S J
SJ
Burakoff
D V
DV
Faller
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis; D002472:Cell Transformation, Viral / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D005260:Female; D005347:Fibroblasts / Q000276:immunology; D006183:H-2 Antigens / Q000032:analysis*; D007113:Immunity, Innate; D007372:Interferons / Q000494:pharmacology; D007942:Leukemia, Experimental / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008979:Moloney murine leukemia virus / Q000276:immunology; D008980:Moloney murine sarcoma virus / Q000276:immunology; D012367:RNA, Viral / Q000032:analysis; D012513:Sarcoma, Experimental / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D001613:beta 2-Microglobulin / Q000032:analysis
D000956:Antigens, Viral; D006183:H-2 Antigens; D012367:RNA, Viral; D001613:beta 2-Microglobulin; D007372:Interferons