Indirect allorecognition in solid organ transplantation.
Recipient T cell recognition of donor major histocompatibility complex (MHC) alloantigens plays a central role in both acute and chronic rejection of human organ allografts. Two different pathways of T cell recognition of donor MHC alloantigens have been described. The direct pathway involves T cell recognition of intact MHC molecules expressed by donor antigen-presenting cells (APCs). The second, or indirect pathway, operates via T helper cell recognition of peptides derived from the processing and presentation of allogeneic MHC molecules on self-APCs. At the onset of primary acute rejection, recipient CD4+ 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.
Department of Pathology, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.
P E
PE
Harris
R
R
Cortesini
N
N
Suciu-Foca
D000818:Animals; D006084:Graft Rejection / Q000276:immunology; D006801:Humans; D007519:Isoantigens; D008285:Major Histocompatibility Complex; D016377:Organ Transplantation; D014181:Transplantation Immunology; D014184:Transplantation, Homologous
D007519:Isoantigens