Induction of T cell responses to a self-antigen following allotransplantation

T cell tolerance to self-antigens is established through the recognition by immature T cells of dominant self-peptides presented in association with self-MHC molecules in the developing thymus (negative selection). 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 with allogeneic B10.A (H2(a)) splenocytes led to an autoimmune T cell response 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 (H2(b)) splenocytes into BALB/c recipients. In addition, we provide evidence indicating that the breakdown of tolerance to D-d 61-80 self-peptide 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 cell responses to donor antigens could spread to crossreactive determinants on self-proteins, thus perpetuating and amplifying the rejection process and presumably initiating tissue-specific autoimmune disorders.