MHC class II hierarchy of superantigen presentation predicts efficiency of infection with mouse mammary tumor virus.
Superantigens (SAgs) encoded by infectious mouse mammary tumor viruses (MMTVs) play a crucial role in the viral life cycle. Their expression by infected B cells induces a proliferative immune response by SAg-reactive T cells which amplifies MMTV infection. This response most likely ensures stable MMTV infection and transmission to the mammary gland. Since T cell reactivity to SAgs from endogenous Mtv loci depends on MHC class II molecules expressed by B cells, we have determined the ability of MMTV to infect various MHC congenic mice. We show that MHC class II I-E+ compared with I-E- mouse strains show higher levels of MMTV infection, most likely due to their ability to induce a vigorous SAg-dependent immune response following MMTV encounter. Inefficient infection is observed in MHC class II I-E- mice, which have been shown to present endogenous SAgs poorly. Therefore, during MMTV infection the differential ability of MHC class II molecules to form a functional complex with SAg determines the magnitude of the proliferative response of SAg-reactive T cells. This in turn influences the degree of T cell help provided to infected B cells and therefore the efficiency of amplification of MMTV infection.
Held
W
W
Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
Waanders
G A
GA
MacDonald
H R
HR
Acha-Orbea
H
H
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D005434:Flow Cytometry; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology*; D008297:Male; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008822:Mice, Transgenic; D016133:Polymerase Chain Reaction; D012192:Retroviridae Infections / Q000276:immunology*; D018089:Superantigens / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D014412:Tumor Virus Infections / Q000276:immunology*
D004279:DNA, Viral; D000949:Histocompatibility Antigens Class II; D018089:Superantigens