Recognition of a tissue-specific polymorphism by graft infiltrating T-cell clones isolated from a renal allograft with acute rejection

Abstract

Acute interstitial rejection is an important clinical problem after cadaver kidney transplantation. Recently we have reported that six of 17 graft-infiltrating cell (GIC) lines isolated from kidneys undergoing such rejection episodes recognize graft-derived proximal tubular cells but not lymphoid cells from the same donor. In this study we characterized the specificity of one such GIC line in more detail. From this T-cell line, 18 cytotoxic T-cell (CTL) clones were isolated. Four of these were also cytotoxic against donor lymphoid cells. Nine tissue-specific clones were selected for further analysis. They all contained CD8+ and TCR alpha/beta+ cells and cytotoxicity by these cells was class I restricted. Only proximal tubular epithelial cells (PTEC) expressing HLA-A31 (an antigen present in the donor but absent in the recipient) were recognized by all clones. There were, however, three clones that did not lyse all HLA-A31+ PTEC lines, demonstrating recognition of an HLA-A31 tissue-associated polymorphism. Thus during rejection episodes after renal transplantation GIC may recognize various tissue-derived peptides bound to a mismatched HLA molecule on the cell surface of renal parenchymal cells. These GIC are likely to contribute to the observed destruction of tubuli during episodes of acute rejection after kidney transplantation.