Intramolecular and intermolecular spreading during the course of organ allograft rejection

Immunol Rev. 1998 Aug:164:241-6. doi: 10.1111/j.1600-065x.1998.tb01224.x.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Graft Rejection / immunology*
  • HLA Antigens / immunology*
  • HLA-DR Antigens / immunology
  • Humans
  • Isoantigens
  • Major Histocompatibility Complex*
  • Transplantation, Homologous


  • HLA Antigens
  • HLA-DR Antigens
  • Isoantigens