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Mycoplasma arthritidis mitogen. V beta engaged in mice, rats, and humans, and requirement of HLA-DR alpha for
R Baccala1, L R Smith, M Vestberg
1Department of Immunology, Research Institute of Scripps Clinic, La Jolla, California 92037.
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.
Insights
Mycoplasma arthritidis mitogen (MAM) engages specific T cell V beta chains in mice, rats, and humans. This superantigen activity, primarily presented by DR alpha, suggests limited involvement in autoimmune diseases linked to DR haplotypes.
Area of Science:
- Immunology
- T cell biology
- Superantigen research
Background:
- Mycoplasma arthritidis mitogen (MAM) is a T cell mitogen for multiple species.
- MAM acts as a superantigen in mice, binding I-E molecules and activating specific T cell receptor V beta chains.
- Understanding the V beta engagement spectrum of MAM is crucial for its role in immunology.
Purpose of the Study:
- To fully characterize the V beta-engaging activities of MAM in mice.
- To define the V beta-engaging activities of MAM in rats and humans.
- To elucidate the presentation mechanisms of MAM in T cell activation.
Main Methods:
- Utilized multiprobe RNase-protection assays.
- Employed mice transgenic for human DR alpha, DR beta, and DR alpha beta.
- Analyzed V beta usage in response to MAM in different species.
Main Results:
- Identified MAM-reactive V beta in mice (V beta 5.1, V beta 6, V beta 8.1-8.3).
- Documented V beta engagement in rats (V beta 5.1, V beta 6, V beta 8.1-8.2) and humans (primarily V beta 19.1, with others).
- Showed DR alpha mediates MAM presentation and V beta engagement in transgenic mice.
Conclusions:
- MAM engages homologous V beta chains across species, suggesting conserved binding sites.
- MAM presentation via nonpolymorphic DR alpha makes its role in DR-associated autoimmune diseases unlikely.
- Superantigen-activated T cells could potentially cross-react with self-antigens, contributing to disease.