Intramolecular and intermolecular spreading during the course of organ allograft rejection.

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 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.

journal_name

Immunol Rev

journal_title

Immunological reviews

authors

Suciu-Foca N,Harris PE,Cortesini R

doi

10.1111/j.1600-065x.1998.tb01224.x

subject

Has Abstract

pub_date

1998-08-01 00:00:00

pages

241-6

eissn

0105-2896

issn

1600-065X

journal_volume

164

pub_type

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