Response of Vβ8.1+ 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 Vβ8.1 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 Vβ8.1 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 Vβ8.1 transgenic mice by stimulation of lymph node T cells with C57BL/6 alloantlgens. Interestingly, CD4+CD8−Vβ8.1+ 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 cytoklne 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 antl-CD4 antibody on the proliferatlve 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