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PMID: 7722447 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Susceptibility to tumors induced by polyoma virus is conferred by an endogenous mouse mammary tumor virus superantigen.

The Journal of experimental medicine ·Vol. 181 ·No. 5 ·1995-05-01 ·Pages 1683-92

Lukacher AE, Ma Y, Carroll JP, Abromson-Leeman SR, Laning JC, Dorf ME, Benjamin TL

Abstract

A dominant gene carried in certain inbred mouse strains confers susceptibility to tumors induced by polyoma virus. This gene, designated Pyvs, was defined in crosses between the highly susceptible C3H/BiDa strain and the highly resistant but H-2k-identical C57BR/cdJ strain. The resistance of C57BR/cdJ mice is overcome by irradiation, indicating an immunological basis. In F1 x C57BR/cdJ backcross mice, tumor susceptibility cosegregates with Mtv-7, a mouse mammary tumor provirus carried by the C3H/BiDa strain. This suggests that Pyvs might encode the Mtv-7 superantigen (SAG) and abrogate polyoma tumor immunosurveillance through elimination of T cells bearing specific V beta domains. DNA typing of 110 backcross mice showed no evidence of recombination between Pyvs and Mtv-7. Strongly biased usage of V beta 6 by polyoma virus-specific CD8+ cytotoxic T lymphocytes in C57BR/cdJ mice implicates T cells bearing this Mtv-7 SAG-reactive V beta domain as critical anti-polyoma tumor effector cells in vivo. These results indicate identity between Pyvs and Mtv-7 sag, and demonstrate a novel mechanism of inherited susceptibility to virus-induced tumors based on effects of an endogenous superantigen on the host's T cell repertoire.

MeSH Terms
Animals Crosses, Genetic Female Mammary Tumor Virus, Mouse/immunology,isolation & purification Mice Mice, Inbred C3H Mice, Inbred CBA Papillomavirus Infections/genetics,immunology Polyomavirus Proviruses/isolation & purification Receptors, Antigen, T-Cell, alpha-beta/analysis Superantigens/genetics,physiology T-Lymphocytes, Cytotoxic/immunology Tumor Virus Infections/genetics,immunology
Chemicals
Receptors, Antigen, T-Cell, alpha-beta Superantigens
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Lukacher A E
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Ma Y
Carroll J P
Abromson-Leeman S R
Laning J C
Dorf M E
Benjamin T L
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.181.5.1683
Published
1995-05-01
Pages
1683-92
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2191990
Subset
IM
Grants
NCI NIH HHS · R01 CA56057 · United States
NCI NIH HHS · R35 CA44343 · United States
NCI NIH HHS · T32 CA09031 · United States
External Links
PubMed source DOI: 10.1084/jem.181.5.1683 PMC Full Text View journal details
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