Association of a V beta 2-specific superantigen with a tumorigenic milk-borne mouse mammary tumor virus.
A number of endogenous mouse mammary tumor virus (MMTV) proviruses encode superantigens that have the property of stimulating mature T lymphocytes in a TCR V beta-specific fashion and of mediating V beta-specific clonal deletion in developing T cells. The tumorigenic milk-borne MMTV carried by C3H and GR mice also have superantigen properties in vivo, and it has been proposed that this superantigenic function is critical to the infectivity and/or tumorigenicity of the virus. To test the requirement for superantigen properties in tumorigenic MMTV, a highly tumorigenic strain of MMTV isolated from BALB/c mice (BALB/cV virus) was analyzed for its effect on TCR V beta expression. It was found that exposure of newborn mice to milk-borne virus results in marked deletion of V beta 2-expressing CD4+ peripheral T cells. This deletion is detected in mature TCRhigh thymocytes as well as in peripheral T cells from virus-exposed mice. Deletion is dependent on expression of a permissive MHC type in mice exposed to virus. Subcutaneous injection of adult mice with virus-containing milk induces a substantial increase in V beta 2+ CD4+ cells in draining lymph nodes within 4 days. Thus, tumorigenic BALB/cV is associated with V beta 2-specific superantigen activity capable of mediating both T cell expansion and clonal deletion in vivo. These findings are consistent with a critical role of superantigen-mediated T cell activation in MMTV infection and tumorigenesis.
Hodes
R J
RJ
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Novick
M B
MB
Palmer
L D
LD
Knepper
J E
JE
D000818:Animals; D000956:Antigens, Viral / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000032:analysis; D005260:Female; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D008285:Major Histocompatibility Complex; D008325:Mammary Neoplasms, Experimental / Q000276:immunology*; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology; D013997:Time Factors; D014412:Tumor Virus Infections / Q000276:immunology
D000956:Antigens, Viral; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta