Integrin-mediated interactions influence the tissue specificity of CD8+ cytolytic T lymphocytes

Abstract

We previously reported that CD8+ cytotoxic T lymphocytes (CTL) elicited in response to allogeneic renal epithelial cells (anti-REC CTL) preferentially lyse REC targets as compared to conventional lymphoid cell (LC) targets. It is often tacitly assumed that such cell type specificity results from CTL recognition of tissue-restricted MHC/peptide complexes. However, we herein report that anti-REC CTL uniquely express CD103, an integrin with known specificity for the epithelial cell-restricted ligand E-cadherin, and are deficient in expression of CD11a (LFA-1), an integrin known to play a critical accessory role in promoting lysis of LC targets. We demonstrate that CD8+ CTL clones with disparate CD103/CD11a phenotypes but identical specificities for allo-MHC/peptide can exhibit marked differences in cell type specificity. Antibody blocking studies provided direct evidence that CD103 serves as an accessory molecule that promotes lysis of REC targets. Taken together, these data indicate that integrin-mediated accessory interactions can influence the capacity of CD8+ CTL to discriminate between different cell types.