title: Synthetic HLA-A2 derived peptides are recognized and presented in renal graft recipients.
abstract: Indirect presentation of allogeneic MHC antigen is an important pathway by which allografts are rejected and tolerance maintained by regulatory CD4(+) T cells. In this study HLA-A2 derived synthetic peptides were used to determine whether T cells of non-HLA-A2 renal graft recipients, which had been HLA-A2 mismatched to their organ donors, recognize some of the HLA-A2-derived peptides. Among the HLA-A2 mismatched patients, 60% recognized residues 56--69, 65--79, and 75--89. Peripheral blood lymphocytes derived from healthy individuals showed low reactivity towards allopeptides, indicating that sensitization towards HLA-A2 induced response towards HLA-A2 derived peptides. The response to the peptides was blocked by antibodies to HLA-DR, -DQ, and CD4. Depletion of antigen presenting cells abrogated response towards the allopeptides, confirming that the observed proliferation was mediated by the indirect pathway. Interestingly, although none of the HLA-A2 mismatched patients had any signs for either acute or chronic rejection, considerable response to allo-derived HLA-A2 was observed.
authors.affiliation: Institute of Immunology, University of Kiel, Kiel, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Stegmann
authors.forename: A
authors.initials: A
authors.lastname: Müller
authors.forename: N
authors.initials: N
authors.lastname: Zavazava
mesh_terms: D000595:Amino Acid Sequence; D017951:Antigen Presentation / Q000187:drug effects / Q000276:immunology*; D015789:HLA-A2 Antigen / Q000378:metabolism*; D006650:Histocompatibility Testing; D006801:Humans; D006825:Hybridomas; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D020014:K562 Cells; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology* / Q000378:metabolism*; D011184:Postoperative Period; D014407:Tumor Cells, Cultured
chemical_list: D015789:HLA-A2 Antigen; D007166:Immunosuppressive Agents; D010446:Peptide Fragments