Induction of TCR Vβ-specific CD8+ CTLs by TCR Vβ-derived peptides bound to HLA-E

Previous studies have identified murine and human regulatory CD8(+) T cells specific for TCR-V beta families expressed on autologous activated CD4(+) T cells. In the mouse, these regulatory CD8(+) T cells were shown to be restricted by the MHC class Ib molecule, Qa-1. In the present study, we asked whether HLA-E, the human functional equivalent of Qa-1, binds V beta peptides and whether the HLA-E/V beta -peptide complex induces and restricts human CD8(+) CTLs. We first created stable HLA-E gene transfectants of the C1R cell line (C1R-E). Two putative HLA-E binding nonapeptides identified in human TCR V beta1 and V beta2 chains (SLELGDSAL and LLLGPGSGL, respectively) were shown to bind to HLA-E. CD8(+) T cells could be primed in vitro by C1R-E cells loaded with the V beta1 (C1R-E/V1) or V beta2 (C1R-E/V2) peptide to preferentially kill C1R-E cells loaded with the respective inducing V beta peptide, compared with targets loaded with the other peptides. Priming CD8(+) T cells with untreated C1R-E cells did not induce V beta -specific CTLs. Of perhaps more physiological relevance was the finding that the CD8(+) CTLs primed by C1R-E/V1 also preferentially killed activated autologous TCR V beta1(+). Similar results were observed in reciprocal experiments using C1R-E/V2 for priming. Furthermore, anti-CD8 and anti-MHC class I mAbs inhibited this V beta -specific killing of C1R-E and CD4(+) T cell targets. Taken together, the data provide evidence that certain TCR-V beta peptides can be presented by HLA-E to further induce V beta -specific CD8(+) CTLs.