Intramolecular and intermolecular spreading during the course of organ allograft rejection

被引:43
作者
Suciu-Foca, N
Harris, PE
Cortesini, R
机构
[1] Columbia Univ, Coll Phys & Surg, Dept Pathol, Div Immunogenet, New York, NY 10032 USA
[2] Univ Rome La Sapienza, Serv Trapianti Organo, Inst Clin Chirug 2, Dept Surg, Rome, Italy
关键词
D O I
10.1111/j.1600-065X.1998.tb01224.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 KLA-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.
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页码:241 / 246
页数:6
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