Superantigen-induced immune stimulation amplifies mouse mammary tumor virus infection and allows virus transmission.
Endogenous and infectious mouse mammary tumor viruses (MMTVs) encode in their 3' long terminal repeat a protein that exerts superantigen activity; that is, it is able to interact with T cells via the variable domain of the T cell receptor (TCR) beta chain. We show here that transmission of an infectious MMTV is prevented when superantigen-reactive cells are absent through either clonal deletion due to the expression of an endogenous MTV with identical superantigen specificity or exclusion due to expression of a transgenic TCR beta chain that does not interact with the viral superantigen. A strict requirement for superantigen-reactive T cells is also seen for a local immune response following MMTV infection. This immune response locally amplifies the number of MMTV-infected B cells, most likely owing to their clonal expansion. Collectively, our data indicate that a superantigen-induced immune response is critical for the MMTV life cycle.
Held
W
W
Ludwig Institute for Cancer Research, Lausanne Branch, Epalinges, Switzerland.
Waanders
G A
GA
Shakhov
A N
AN
Scarpellino
L
L
Acha-Orbea
H
H
MacDonald
H R
HR
D000818:Animals; D000956:Antigens, Viral / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology; D001483:Base Sequence; D004279:DNA, Viral / Q000235:genetics / Q000302:isolation & purification; D005434:Flow Cytometry; D008198:Lymph Nodes / Q000382:microbiology; D008325:Mammary Neoplasms, Experimental / Q000276:immunology / Q000382:microbiology*; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid; D013601:T-Lymphocytes / Q000276:immunology
D000956:Antigens, Viral; D004279:DNA, Viral; D009838:Oligodeoxyribonucleotides; D016693:Receptors, Antigen, T-Cell, alpha-beta