Cell components required for deletion of an autoreactive T cell repertoire

T cells become tolerant to self antigens during their development in the thymus. Clonal deletion of thymocytes bearing T cell receptor (TcR) which recognize self antigens is a major mechanism for generating tolerance. In the present study we have used allogeneic bone marrow (BM) chimeras, prepared with various combinations of mouse strains and focusing especially on expressions of I-E molecules and Mls-1a antigens on the cell surface, to investigate both immunohistochemically and by flow cytometry the cell components that contribute to the clonal deletion of T cells positive for V beta 6 TcR. The V beta 6 TcR expression is strongly associated with T cell recognition of both I-E and Mls-1a antigens. We found that I-E+ cells derived from donor BM (and thus not of recipient lineage) represented a primary requirement for deletion of Mls-1a-reactive thymocytes which bear V beta 6 TcR. Immunohistochemical analysis revealed that the donor-derived I-E+ cells were distributed mainly to the thymic medulla and that the V beta 6+ cells were eliminated from the thymic medulla between 2 and 3 weeks following BM transplantation. In contrast, Mls-1a+ cells of either donor or recipient origin might be responsible for the deletion, even though cortical epithelial cells appeared not to express Mls-1a antigens.