Mycoplasma arthritidis mitogen. V beta engaged in mice, rats, and humans, and requirement of HLA-DR alpha for presentation. |
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Authors: | R Baccala L R Smith M Vestberg P A Peterson B C Cole A N Theofilopoulos |
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Affiliation: | Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037. |
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Abstract: | OBJECTIVE. Mycoplasma arthritidis mitogen (MAM) is mitogenic for mouse, rat, and human T cells, and behaves as a superantigen in mice through its capacity to bind to the alpha chain of I-E molecules and engage entire sets of T cells expressing specific V beta. Here, we have attempted to fully characterize the V beta-engaging activities of MAM in mice, and define similar activities in rats and humans. METHODS. Multiprobe RNase-protection assays and mice transgenic for human DR alpha, DR beta, and DR alpha beta were utilized for this purpose. RESULTS. MAM-reactive V beta in the mouse included not only the previously reported V beta 6, V beta 8.1, V beta 8.2, and V beta 8.3, but also V beta 5.1. In the rat, engagement of V beta 5.1, V beta 6, V beta 8.1, and V beta 8.2, but not V beta 8.3, was documented, whereas in humans, the engaged V beta included primarily V beta 19.1 (alternatively termed V beta 17.1) and, to a lesser extent, V beta 3.1, V beta 11.1, V beta 12.1, and V beta 13.1. In DR transgenic E alpha- E beta- mice, presentation of MAM and engagement of specific V beta was effected by DR alpha. CONCLUSIONS. Homologous V beta are engaged by MAM in mice, rats, and humans, presumably through a binding site similar to that proposed previously for other superantigens. MAM presentation primarily via the nonpolymorphic DR alpha makes it unlikely that there is involvement of such a superantigen in the pathogenesis of autoimmune diseases known to be associated with certain DR haplotypes. The possibility cannot be excluded, however, that superantigen-activated T cells may lead to disease by cross-reactions with self-antigens presented by particular DR haplotypes. |
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