Premium
Intramolecular and intermolecular spreading during the course of organ allograft rejection
Author(s) -
SuciuFoca Nicole,
Harris Paul E.,
Cortesini Raffaello
Publication year - 1998
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.1998.tb01224.x
Subject(s) - immunology , major histocompatibility complex , epitope , human leukocyte antigen , t cell , biology , antigen , transplantation , histocompatibility , antigen presentation , immune system , medicine
Summary: There are two distinct pathways by which T cells may 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 lo donor HLA‐DR alloantigens are limited to a single dominant determinant present on erne 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 lo 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.