Stimulation of mouse lymphocytes by a mitogen derived from Mycoplasma arthritidis (MAM). VIII. Selective activation of T cells expressing distinct V beta T cell receptors from various strains of mice by the "superantigen" MAM.
Mycoplasma arthritidis T cell mitogen (MAM), in association with its MHC ligand, is recognized by T cells that express TCR-alpha/beta assembled with a product(s) of the V beta 8 gene family. We show here that lymphocytes from mice which fail to express V beta 8 products can also be activated by MAM and the resulting cultures exhibit a marked increase in V beta 6 TCR-bearing cells. Evidence was also obtained that MAM can activate T cells that express all three V beta 8 TCR. The mAb, F23.1, which recognizes all V beta 8 gene products, was strongly inhibitory for MAM-induced proliferation of CBA cells whose T cell repertoire for MAM consists of T cells that express V beta 8.2 and 8.3 TCR. In contrast, the F23.1 mAb was only weakly inhibitory for BALB/c splenocytes which express V beta 6 TCR in addition to all three V beta 8 TCR. Involvement of V beta 8.1, 8.2, 8.3, and V beta 6 in MAM-induced proliferation was confirmed by expanding lymphocyte cultures in the presence of MAM and phenotyping the activated cells for expression of individual V beta TCR. There was also evidence for a selective activation of T cells bearing specific V beta TCR because BALB/c T cell populations expanded with MAM were comprised of 46.2% V beta 8.2+ cells, 18.6% V beta 8.1+ cells, 7.6% V beta 8.3+ cells and 6.7% V beta 6+ cells. Recent studies suggest that the newly described "superantigens" including the staphylococcal enterotoxins and the self minor lymphocyte-stimulating Ag activate T cells in a manner similar to that described earlier for MAM. The discovery of shared recognition of these proteins by specific V beta TCR strongly suggests that MAM belongs to the superantigen protein family, the members of which may share cross-reactive epitopes. Inasmuch as MAM is produced by an organism which induces chronic joint disease, our findings provide the basis for a new model to study the role of superantigens in the development of chronic autoimmune type diseases.
Cole
B C
BC
Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City 84132.
Kartchner
D R
DR
Wells
D J
DJ
D000818:Animals; D000911:Antibodies, Monoclonal; D000941:Antigens; D000942:Antigens, Bacterial; D007158:Immunologic Techniques; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D008934:Mitogens / Q000276:immunology*; D009174:Mycoplasma / Q000276:immunology*; D011506:Proteins; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology
D000911:Antibodies, Monoclonal; D000941:Antigens; D000942:Antigens, Bacterial; D008934:Mitogens; C052996:Mycoplasma arthritidis mitogen; D011506:Proteins; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens