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-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 V
1 and V
2 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
1
(C1R-E/V1) or V
2 (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 V
1+. 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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