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 role in the rejection of allografts in experimental animals. Although there has been much speculation as to its role in clinical transplantation, especially with regard to chronic rejection, indirect T cell allorecognition has been difficult to demonstrate in transplant patients. In 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 regions of six of the most common HLA class I alleles in Caucasian populations (A1, 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 rejection of heart/lung transplants. The donor-recipient combinations were selected such that at least one of the six HLA antigens above was present in the donor and absent in the recipient. Peripheral blood mononuclear cells from these patients responded strongly in proliferation assays to phytohemagglutinin. However, none responded to the incompatible donor HLA peptides. Compartmentalization of responding T cells, the effects of immunosuppression, and assay sensitivity are discussed as possible explanations for the negative results.
Saleem
M
M
Division of Cell and Molecular Biology, University of London, UK.
Gustafsson
K
K
Fabre
J W
JW
D000328:Adult; D000595:Amino Acid Sequence; D002648:Child; D006084:Graft Rejection / Q000276:immunology*; D015234:HLA-A Antigens / Q000276:immunology*; D015235:HLA-B Antigens / Q000276:immunology*; D016041:Heart-Lung Transplantation / Q000276:immunology*; D006801:Humans; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D015234:HLA-A Antigens; D015235:HLA-B Antigens; D010446:Peptide Fragments