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 Dd 61-80 is dominant in syngeneic BALB/c mice (H2d). T cell tolerance to Dd 61-80 in this mouse strain resulted in the absence of T cell proliferation following in vivo priming with Dd 61-80 peptide. Here, we show that transplantation of BALB/c mice with allogeneic B10.A (H2a) splenocytes led to an autoimmune T cell response toward the dominant self-peptide Dd 61-80. No T cell responses to Dd 61-80 peptide were observed after transplantation of C57BL/6 (H2b) splenocytes into BALB/c recipients. In addition, we provide evidence indicating that the breakdown of tolerance to Dd 61-80 self-peptide resulted from the presentation of the donor crossreactive peptide Kk 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.
Fedoseyeva
E V
EV
Immunogenetics and Transplantation Laboratory, Department of Surgery, University of California San Francisco, California 94143-0508 USA.
Tam
R C
RC
Popov
I A
IA
Orr
P L
PL
Garovoy
M R
MR
Benichou
G
G
D000595:Amino Acid Sequence; D000818:Animals; D001324:Autoantigens / Q000276:immunology*; D001327:Autoimmune Diseases / Q000209:etiology; D006084:Graft Rejection; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D007108:Immune Tolerance; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014184:Transplantation, Homologous / Q000276:immunology*
D001324:Autoantigens; D015395:Histocompatibility Antigens Class I; D010446:Peptide Fragments