Paracrine transfer of mouse mammary tumor virus superantigen.
Transfer of vSAG7, the endogenous superantigen encoded in the Mtv7 locus, from MHC class II to MHC class II+ cells has been suggested to occur both in vivo and in vitro. This transfer usually leads to the activation and deletion of T cells expressing responsive V beta s. However, there is no direct molecular evidence for such a transfer. We have developed an in vitro system which confirms this property of vSAGs. vSAG7 was transfected into a class II murine fibroblastic line. Coculture of these cells with class II+ cells and murine T cell hybridomas expressing the specific V beta s led to high levels of IL-2 production which was specifically inhibited by vSAG7- and MHC class II-specific mAbs. Moreover, injection of vSAG7+ class II+ cells in mice led to expansion of V beta 6+ CD4+ cells. We show that this transfer activity is paracrine but does not require cell-to-cell contact. Indeed, vSAG7 was transferred across semi-permeable membranes. Transfer can occur both from class II+ and class II+ cells, indicating that MHC class II does not sequester vSAG7. Finally, competition experiments using bacterial toxins with well defined binding sites showed that the transferred vSAG7 fragment binds to the alpha 1 domain of HLA-DR.
Delcourt
M
M
Laboratoire d'Immunologie Institut de Recherches Cliniques de Montréal, Canada.
Thibodeau
J
J
Denis
F
F
Sekaly
R P
RP
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D002450:Cell Communication; D002460:Cell Line; D004768:Enterotoxins / Q000378:metabolism; D005260:Female; D006684:HLA-DR Antigens / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000502:physiology; D006801:Humans; D008213:Lymphocyte Activation; D008324:Mammary Tumor Virus, Mouse / Q000276:immunology*; D051379:Mice; D008808:Mice, Inbred CBA; D018089:Superantigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
D000911:Antibodies, Monoclonal; D004768:Enterotoxins; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal