Wild-derived inbred mice have a novel basis of susceptibility to polyomavirus-induced tumors.
Polyomavirus induces a broad array of tumors when introduced into newborn mice of certain standard inbred strains, notably those bearing the H-2(k) haplotype. Susceptibility in these mice is conferred by an endogenous mouse mammary tumor virus superantigen (Mtv-7 sag) that acts to delete T cells required for polyomavirus-induced tumor immunosurveillance. In the present study we show that mice of two wild-derived inbred strains, PERA/Ei (PE) and CZECH II/Ei (CZ), are highly susceptible to polyomavirus but carry no detectable Mtv sag-related sequences and show no evidence of Vbeta deletion. C57BR/cdJ (BR) mice, which are H-2(k) but lack the endogenous Mtv-7, are highly resistant based on an effective anti-polyomavirus tumor immune response. When crossed with BR, both PE and CZ mice transmit their susceptibility in a dominant fashion, indicating a mechanism(s) that overrides the immune response of BR. Susceptibility in PE and CZ mice is not based on interference with antigen processing or presentation since cytotoxic T cells from BR can efficiently kill F(1)-derived tumor cells in vitro. The expected precursors of polyomavirus-specific cytotoxic T cells are present in both the wild inbred animals and their F(1) progeny. These findings indicate a novel basis of susceptibility that operates independently of endogenous superantigen and prevents the development of tumor immunity.
Velupillai
P
P
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Yoshizawa
I
I
Dey
D C
DC
Nahill
S R
SR
Carroll
J P
JP
Bronson
R T
RT
Benjamin
T L
TL
D000818:Animals; D000835:Animals, Wild; D017951:Antigen Presentation / Q000276:immunology; D000956:Antigens, Viral; D004198:Disease Susceptibility / Q000276:immunology; D008562:Membrane Glycoproteins / Q000276:immunology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D011120:Polyomavirus / Q000276:immunology*; D027601:Polyomavirus Infections / Q000276:immunology*; D014412:Tumor Virus Infections / Q000276:immunology*
D000956:Antigens, Viral; D008562:Membrane Glycoproteins; C095378:Mtv-7 superantigen, Mouse mammary tumor virus