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- Title
Intramolecular and intermolecular spreading during the course of organ allograft rejection.
- Authors
Sucui-Foca, Nicole; Harris, Paul E.; Cortesini, Rafaello
- Abstract
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 an chronic rejection of human organ allografts. Our studies have shown that, at the onset or 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.
- Subjects
T cells; MOLECULES; PEPTIDES; ANTIGENS
- Publication
Immunological Reviews, 1998, Vol 164, Issue 1, p241
- ISSN
0105-2896
- Publication type
Article
- DOI
10.1111/j.1600-065X.1998.tb01224.x