Loss of endogenous mouse mammary tumor virus superantigen increases tumor resistance.
From a cross between a tumor-susceptible mouse strain (DBA/2; D) and a tumor-resistant MHC-identical strain (B10.D2; D2) new recombinant inbred mouse strains were established over many generations of inbreeding and tumor resistance selection. Since resistance to the highly metastatic DBA/2 lymphoma variant ESb had an immunologic basis, and the two parental strains differed in endogenous viral superantigens (vSAGs), DNA of three D2 x D recombinant inbred mouse lines was typed for endogenous mouse mammary tumor viruses using mouse mammary tumor virus long terminal repeat- and env gene-specific probes. The resistant D2 x D mice were very similar to the susceptible parental strain D in their Mtv Southern blots, except for the lack of a single band corresponding to Mtv-7, the provirus coding for the strong DBA/2 superantigen Mls-1a. A backcross analysis revealed that Mtv-7-negative F2 mice were significantly more resistant than Mtv-7-positive F2 mice. When Mtv-7 was reintroduced into the resistant lines by crossing them with either CBA/J or BALB/D2.Mls-1a, the mice became again more tumor susceptible. Finally, we demonstrate the ability to transfer immunoresistance and graft-vs-leukemia reactivity from tumor-resistant to tumor-susceptible mice.
Division of Cellular Immunology, German Cancer Research Center, Heidelberg. v.schirrmacher@dkfz-heidelberg.de
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Schirrmacher
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Beutner
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Bucur
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Umansky
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Rocha
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von Hoegen
D000818:Animals; D000956:Antigens, Viral / Q000235:genetics*; D003433:Crosses, Genetic; D004279:DNA, Viral / Q000032:analysis; D004198:Disease Susceptibility; D006087:Graft vs Host Reaction / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate; D016399:Lymphoma, T-Cell; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics* / Q000276:immunology* / Q000302:isolation & purification; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D011533:Proviruses / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D012192:Retroviridae Infections / Q000235:genetics / Q000276:immunology; D018089:Superantigens / Q000235:genetics*; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000235:genetics / Q000276:immunology
D000956:Antigens, Viral; D004279:DNA, Viral; D018089:Superantigens