Kidney cell-restricted recognition of MHC class I alloantigens by human cytolytic T cell clones

The kidney expresses antigens not generally expressed by other cells in the body. To test the hypothesis that kidney-restricted antigens alter T cell recognition of MHC class I alloantigens, a panel of human T cell clones was established using an allogeneic kidney cell line (KCL) as the source of stimulator cells. Unexpectedly, a majority of these clones lysed the stimulating KCL in an allospecific manner but completely failed to lyse lymphoid cell targets derived from the KCL donor. Three of the KCL-reactive clones have been characterized in detail. All three are CD8+/CD4-, alpha/beta TCR,+ and their lytic activity is blocked by monoclonals to HLA class I framework determinants. Mapping studies using a panel of KCL targets, and blocking studies with allele-specific monoclonals indicated that clone 1-5 is directed to HLA-A3, clone 3-10 to HLA-B62 (putatively), and clone 5-2 to HLA-B51. Direct lysis and cold target inhibition assays demonstrated that clones 1-5 and 3-10 recognize their target class I alloantigens on KCL but not on EBV-transformed B cells or PHA-stimulated T cells. FACS analysis and HLA phenotyping excluded quantitative or qualitative deficiencies in HLA class I expression on the lymphoid cell targets as likely mechanisms of tissue specificity. These data suggest that kidney-restricted antigens may play a role in T cell recognition of MHC class I alloantigens, and they raise the possibility that parenchymal cell-restricted effector populations may contribute to rejection of renal allografts.