T lymphocyte cloning from rejected human kidney allograft. Recognition repertoire of alloreactive T cell clones.

Abstract

We analyzed the recognition repertoire of 16 human alloreactive T cell clones (ATLC) derived from cells invading an irreversibly rejected kidney allograft. These clones, which specifically proliferated against the kidney donor B lymphoblastoid cell line, fell into two classes: CD4+ killers and CD8+ killers. Cytotoxic and proliferative activities of the ATLC were studied by using a panel of allogeneic cells sharing HLA specificities with kidney donor cells. Moreover, mAb recognizing monomorphic parts of HLA class I and class II molecules were used in blocking experiments of ATLC cytotoxicity. The results obtained from proliferative and cytotoxic assays were concordant. All ATLC investigated were directed against HLA molecules, and some clones were found to recognize HLA-B, -C, -DP, -DQ, or -DR products. All anti-HLA class I ATLC were CD8+, whereas both CD4+ and CD8+ ATLC were committed against HLA class II specificities. Nine of 16 ATLC were shown to react against serologically defined donor HLA determinants. These data indicate the recognition of HLA determinants in the course of an in vivo alloimmune response and particularly emphasize the role of HLA-C and DP loci products so far ignored in clinical transplantation.