INDUCTION OF T-CELL RESPONSES TO A SELF-ANTIGEN FOLLOWING ALLOTRANSPLANTATION

T cell tolerance to self-antigens is established through the recogniti on by immature T cells of dominant self-peptides presented in associat ion with self-MHC molecules in the developing thymus (negative selecti on). The self-peptide D-d 61-80 is dominant in syngeneic BALB/c mice ( H2(d)), T cell tolerance to D-d 61-80 in this mouse strain resulted in the absence of T cell proliferation following in vivo priming with D- d 61-80 peptide, Here, we show that transplantation of BALB/c mice wit h allogeneic B10.A (H2(a)) splenocytes led to an autoimmune T cell res ponse toward the dominant self-peptide D-d 61-80, NO T cell responses to D-d 61-80 peptide were observed after transplantation of C57BL/6 (H 2(b)) splenocytes into BALB/c recipients. In addition, we provide evid ence indicating that the breakdown of tolerance to D-d 61-80 self-pept ide resulted from the presentation of the donor crossreactive peptide K-k 61-80 at the surface of recipient antigen-presenting cells, Taken together, our results suggest that following allotransplantation, T ce ll responses to donor antigens could spread to crossreactive determina nts on self-proteins, thus perpetuating and amplifying the rejection p rocess and presumably initiating tissue-specific autoimmune disorders.