ATTEMPTS TO DEMONSTRATE INDIRECT T-CELL ALLORECOGNITION OF DONOR MHC PEPTIDES IN TRANSPLANT PATIENTS

Indirect T cell allorecognition has been shown to play an important ro le in the rejection of allografts in experimental animals. Although th ere has been much speculation as to its role in clinical transplantati on, especially with regard to chronic rejection, indirect T cell allor ecognition has been difficult to demonstrate in transplant patients. r n this paper, we looked for in vitro T cell proliferation to synthetic peptides corresponding to donor HLA-A and HLA-B incompatible antigens . Twelve 15 amino acid peptides corresponding to the hypervariable reg ions of six of the most common HLA class I alleles in Caucasian popula tions (Al, A2, A3, B7, B8 and B44) were studied. Blood was taken from 12 adult patients following one or more episodes of acute kidney graft rejection, and from three pediatric patients undergoing chronic rejec tion of heart/lung transplants. The donor-recipient combinations were selected such that at least one of the six HLA antigens above was pres ent in the donor and absent in the recipient. Peripheral blood mononuc lear cells from these patients responded strongly in proliferation ass ays to phytohemagglutinin. However, none responded to the incompatible donor HLA peptides. Compartmentalization of responding T cells, the e ffects of immunosuppression, and assay sensitivity are discussed as po ssible explanations for the negative results. Copyright (C) 1996 Elsev ier Science B.V.