New approaches to specific immunomodulation in transplantation.
T cells can recognize foreign MHC antigens by two distinct routes, either directly as intact molecules, or indirectly as processed peptides. Recent evidence strongly suggests that the indirect pathway of allorecognition plays a key role in initiating and sustaining graft rejection. Theoretically, all mismatched HLA alloantigens could generate immunogenic peptides which may be recognized in the context of any of the two self HLA-DR molecules. However, indirect recognition appears to be limited to a single peptide determinant of an allogeneic HLA-DR molecule and restricted by one self HLA-DR molecule. Furthermore, T cells involved in the self-restricted allopeptide recognition express a limited array of T cell receptor variable genes. These findings suggest that selective immune interventions, such as peptide blockade of the self HLA-DR molecule involved in the presentation of the dominant allopeptide, induction of high-zone tolerance or TCR antagonism, may be devised to prevent graft rejection.
Colovai
A I
AI
College of Physicians & Surgeons of Columbia University, Department of Pathology, New York, New York 10032, USA.
Molajoni
E R
ER
Cortesini
R
R
Suciu-Foca
N
N
D017951:Antigen Presentation; D018604:Epitope Mapping; D006084:Graft Rejection / Q000276:immunology; D006684:HLA-DR Antigens / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D016056:Immunodominant Epitopes / Q000276:immunology; D007165:Immunosuppression Therapy; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D016378:Tissue Transplantation; D014181:Transplantation Immunology
D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D016056:Immunodominant Epitopes; D011948:Receptors, Antigen, T-Cell