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Laboratoire d'Immunochimie Analytique, Institut Pasteur, 75015 Paris, France; and
Department of Microbiology and Immunology, Universite de Montréal, H3C 3J7 Montréal, Canada and Department of Microbiology and Immunology, and Department of Experimental Medicine, McGill University, H3A 2B4 Montréal, Canada
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 Vβs. 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 Vβs 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 Vβ6+ 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
1 domain of HLA-DR.
This work was supported by grants RG-544/95 from Human Frontier Science Project, MT-10055 from Medical Research Council of Canada, and 007273 from National Cancer Institute of Canada, attributed to R.P. Sékaly. R.P. Sékaly holds an MRC scientist award. F. Denis and J. Thibodeau are supported by fellowships from National Health Research and Development Program. M. Delcourt has a French government Assistant Moniteur Normalien fellowship.
1Abbreviations used in this paper: MMTV, mouse mammary tumor virus; SAC, splenic adherent cell; SAG, superantigens; SEA SEB, staphylococcal enterotoxia A/B; vSAG, viral superantigen.
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