Mycoplasma arthritidis mitogen. V_β engaged in mice, rats, and humans, and requirement of HLA‐DRα for presentation

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 (Y chain of I-E molecules and engage entire sets of T cells expressing specific Vp. Here, we have attempted to fully characterize the V,-engaging activities of MAM in mice, and define similar activities in rats and humans.Methods. Multiprobe RNase-protection assays and mice transgenic for human DRcu, DRP, and DRaP were utilized for this purpose.Results. MAM-reactive V ' in the mouse included not only the previously reported V&, Vp8.1, Vp8.2, and V9.3, but also V,5.1. In the rat, engagement of Vs.1, V&, V9.1, and V'8.2, but not Vp8.3, was documented, whereas in humans, the engaged V , included primarily V,19.1 (alternatively termed V'17.1) and, to a lesser ~.. Publication No. 7007-1MM from the

Zinc-binding Sites in the N Terminus of Mycoplasma arthritidis-derived Mitogen Permit the Dimer Formation Required for High Affinity Binding to HLA-DR and for T Cell Activation

“…Results from competitive binding assays also reveal cross-inhibition between TSST-1, which is known to span the peptide groove, and MAMwt (38). MAM dimers presented to T cells interact with human V␤ regions 19.1 (alternatively termed V␤ 17.1), 3.1, 11.1, 12.1, and V␤ 13.1 in vitro (61). However, MAM also interacts with the T cell complementary determination region 3, indicating that, while an appropriate V␤ region is present on a TCR, MAM may not activate the T cell unless appropriately stabilized through an interaction with complementary determination region 3 (15).…”

Coexpression of TLR2 or TLR4 with HLA-DR Potentiates the Superantigenic Activities ofMycoplasma arthritidis–Derived Mitogen

“…It is well established that MAM, like other Sags, bind to MHC class II molecules on APCs and is presented as such to T cells by interacting with their TCR, and more specifically with the region Vb 3.1, 13.1, 14, and 17 in humans and Vb 6, 8.1, and 5.1 in mice (38). MAM induces different Vb repertoires depending on the HLA-DR haplotype, which indicates that the Vb specificity of MAM is determined by the MAM/HLA-DR complex (39,40).…”

Association ofMycoplasma arthritidisMitogen with Lethal Toxicity but Not with Arthritis in Mice

“…Antibody against MAM has also been detected in sera from patients with rheumatic diseases (39). The major T-cell subset identified in the synovium of several human rheumatoid arthritis patients expressed the exact V ␤ that has been found to be responsive to MAM (1,32). It has also been demonstrated that MAM can stimulate human T-cell proliferation (2), promote human B-cell differentiation (24), and upregulate human NK cell activity (26).…”