Involvement of Multiple Factors in the Clonal Deletion of Self-Reactive T Cells

Self-tolerance is primarily induced by the elimination of potentially self-reactive T cells during early development of the T cell repertoire. In the mouse, endogenous mouse mammary tumor viruses (MMTV), including minor lymphocyte-stimulating antigens and milk-transmitted exogenous MMTV, have been known to function as self-antigens inducing the clonal deletion of selfreactive T cells in a Vβ-specific manner. We investigated the factors involved in the deletion of Vβ17a-bearing T cells. The results indicated that in addition to the previously reported Vβ17a deletion ligand, Mtv-3, there is a nonmilkborne gene product which progressively deletes Vβ17a (and Vβ3)-bearing T cells during aging. This suggests that clonal deletion is mediated by multiple factors and that a clonal deletion element associated with aging may play a significant role in shaping the T cell repertoire.