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Induction of TCR V-Specific CD8⁺ CTLs by TCR V-Derived Peptides Bound to HLA-E¹

Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032

Previous studies have identified murine and human regulatory CD8⁺ T cells specific for TCR-V 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 peptides and whether the HLA-E/V-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 V1 and V2 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 V1 (C1R-E/V1) or V2 (C1R-E/V2) peptide to preferentially kill C1R-E cells loaded with the respective inducing V peptide, compared with targets loaded with the other peptides. Priming CD8⁺ T cells with untreated C1R-E cells did not induce V-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 V1⁺. 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-specific killing of C1R-E and CD4⁺ T cell targets. Taken together, the data provide evidence that certain TCR-V peptides can be presented by HLA-E to further induce V-specific CD8⁺ CTLs.

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