Response of V beta 8.1+ T cell clones to self Mls-1a: implications for the origin of autoreactive T cells.
Clonal deletion and anergy are two major mechanisms of self-tolerance. However, the molecular mechanisms underlying clonal deletion and anergy, as well as the threshold of TCR affinity/avidity required for these processes, are not known. Expression of the V beta 8.1 TCR correlates with the reactivity of the T cells to the minor lymphocyte stimulating locus-1a (Mls-1a) and T cells expressing this TCR are deleted in the thymus of Mls-1a mice. Similarly, in TCR V beta 8.1 transgenic mice, the number of CD4+CD8-T cells is reduced in Mls-1a mice. However, small numbers of CD4+CD8-T cells remain in the periphery of adult Mls-1a transgenic mice. We have generated T cell clones from TCR V beta 8.1 transgenic mice by stimulation of lymph node T cells with C57BL/6 alloantigens. Interestingly, CD4+CD8-V beta 8.1+ clones isolated from the transgenic mice of Mls-1a background responded to the self-antigen Mls-1a, to which they did not respond in primary assay. Reactive patterns of the clones were compared with clones derived from Mls-1b mice. Proliferation and cytokine production of the clones from Mls-1a mice to the self-antigen Mls-1a were generally reduced when compared with clones from Mls-1b mice. More importantly, T cell clones from Mls-1a mice required more Mls-1a antigen for their activation, and were more susceptible to the inhibitory effects of anti-CD4 antibody on the proliferative responses to Mls-1a than those from Mls-1b mice. These results suggest that the T cell receptor on clones derived from Mls-1a mice have functional but reduced affinity/avidity for self-antigen Mls-1a.
Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia 19104-6082.
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Yui
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Katsumata
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Komori
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Gill-Morse
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Greene
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology; D015551:Autoimmunity; D018801:CD2 Antigens; D015704:CD4 Antigens / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002999:Clone Cells; D005434:Flow Cytometry; D007378:Interleukins / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D016747:Minor Lymphocyte Stimulatory Antigens / Q000276:immunology; D016744:Minor Lymphocyte Stimulatory Loci / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology*; D011971:Receptors, Immunologic / Q000502:physiology
D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D015704:CD4 Antigens; D007378:Interleukins; D007519:Isoantigens; D016169:Lymphocyte Function-Associated Antigen-1; D016747:Minor Lymphocyte Stimulatory Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D011971:Receptors, Immunologic