Intramolecular and intermolecular spreading during the course of organ allograft rejection.
There are two distinct pathways by which T cells may recognize MHC alloantigens. The direct pathway involves T-cell recognition of intact MHC molecules expressed by donor antigen-presenting cells (APCs). The second, or indirect, pathway describes T-cell recognition of peptides derived from the processing and presentation of allogeneic MHC molecules on self APCs. Recent data demonstrates that indirect recognition plays a central role in both acute and chronic rejection of human organ allografts. Our studies have shown that, at the onset of primary acute rejection, recipient T-cell responses to donor HLA-DR alloantigens are limited to a single dominant determinant present on one of the disparate alloantigens and restricted by one of the responder's HLA-DR molecules. In allograft recipients with recurring episodes of rejection, and/or at the onset of chronic rejection, recipient T-cell reactivity may spread to other epitopes within the allogeneic MHC molecule as well as to other alloantigens expressed by graft tissue. Both quantitative and qualitative alterations in T-cell allopeptide reactivity are associated with increased risk of cellular and/or humoral rejection. These studies provide a basis for the design of new therapeutic strategies and for immunologic monitoring of transplant recipients.
Suciu-Foca
N
N
Department of Pathology, Columbia University, New York, USA. suciu_foca@cuccfa.ccc.columbia.edu
Harris
P E
PE
Cortesini
R
R
D006084:Graft Rejection / Q000276:immunology*; D006680:HLA Antigens / Q000276:immunology*; D006684:HLA-DR Antigens / Q000276:immunology; D006801:Humans; D007519:Isoantigens; D008285:Major Histocompatibility Complex; D014184:Transplantation, Homologous
D006680:HLA Antigens; D006684:HLA-DR Antigens; D007519:Isoantigens