Abstract
Abstract To understand tolerance mechanisms to tissue-specific antigens, we probed the development of polyclonal T cells specific for myelin oligodendrocyte glycoprotein (MOG), a myelin antigen targeted during autoimmune demyelinating disease. We find T cell tolerance occurs via two thymocyte selection processes. First, the presence of tissue-specific antigen intrinsically broadens the TCR repertoire to lower overall reactivity of effector T cells. Second, expression of MOG extrinsically induces a higher frequency of more efficacious antigen-specific Foxp3+ regulatory T cell population that prevents autoimmunity. Interestingly, clonal deletion mediated by thymocyte negative selection of high-affinity T cells was not apparent. Thus, cooperative tolerance exists to prevent autoimmunity towards tissue-specific antigens.
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