MYCOPLASMA-ARTHRITIDIS MITOGEN - V-BETA ENGAGED IN MICE, RATS, AND HUMANS, AND REQUIREMENT OF HLA-DR-ALPHA FOR PRESENTATION

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.