Alloreactive anti-HLA-B7 cytolytic T cell clones use restricted T cell receptor genes

Most alloreactive T cells specifically recognize peptides bound to donor MHC molecules. In addition to peptides, solvent accessible MHC residues also may stimulate alloreactive T cells. We studied T cell receptor (TCR) usage by 16 independent anti-HLA-B7 alloreactive cytolytic T lymphocyte (CTL) clones. Most or all of these CTL clones recognized unique peptides bound to HLA-B7. Despite the diversity of peptides recognized, 11 out of 15 CTL clones analyzed expressed TCR V(α) gene segment (AV) subgroups 1 and 3. Within AV subgroup 1, four of six clones expressed AV2; within AV subgroup 3, three clones used AV6. Ten of 14 CTL clones analyzed expressed V(β) gene segment (BV) subgroups 4 and 1. In subgroup 4, BV14 was expressed by four of five alloreactive CTL clones. Similar AV and BV usage restriction was not found in mitogen-stimulated peripheral blood T cells from the major donor of the CTL clones. TCR A and TCR B junctional region sequences were quite diverse in length and sequence, although two CTL clones expressed nearly identical TCR B chains. We found no correlation between TCR AV or TCR BV usage and CTL recognition of 81 HLA-B7 variants. These results are consistent with models of TCR structure, in which very diverse TCR CDR3 regions contact very diverse peptides, and moderately diverse TCR CDR1 and CDR2 regions contact moderately diverse MHC α-helices.