Induction of TCR Vβ-specific CD8+ CTLs by TCR Vβ-derived peptides bound to HLA-E
Induction of TCR Vβ-specific CD8+ CTLs by TCR Vβ-derived peptides bound to HLA-E
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DOI：
10.4049/jimmunol.167.7.3800
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发表时间：
2001-10-01
影响因子：
4.4
通讯作者：
Chess, L
中科院分区：
文献类型：
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作者：
Li, JF;Goldstein, I;Chess, L
先前的研究已经鉴定了对自体活化的CD 4（+）T细胞上表达的TCR-V β家族具有特异性的鼠和人调节性CD 8（+）T细胞。在小鼠中，这些调节性CD 8（+）T细胞被证明受到MHC Ib类分子Qa-1的限制。在本研究中，我们询问了HLA-E（Qa-1的人类功能等同物）是否结合V β肽，以及HLA-E/V β肽复合物是否诱导和限制人类CD 8（+）CTL。我们首先建立了C1 R细胞系（C1 R-E）的稳定HLA-E基因转染子。在人TCR V β 1和V β 2链中鉴定的两种推定的HLA-E结合九肽（分别为SLELGDSAL和LLLGPGSGL）显示与HLA-E结合。CD 8（+）T细胞可以在体外被加载有V β 1（C1 R-E/V1）或V β 2（C1 R-E/V2）肽的C1 R-E细胞致敏，以与加载有其他肽的靶相比优先杀死加载有相应诱导V β肽的C1 R-E细胞。用未处理的C1 R-E细胞引发CD 8（+）T细胞不诱导V β特异性CTL。可能更具有生理相关性的发现是，由C1 R-E/V1引发的CD 8（+）CTL也优先杀死活化的自体TCR V β 1（+）。在使用C1 R-E/V2进行引发的倒数实验中观察到类似的结果。此外，抗-CD 8和抗-MHC I类mAb抑制C1 R-E和CD 4（+）T细胞靶的这种V β特异性杀伤。综上所述，数据提供了某些TCR-V β肽可以由HLA-E呈递以进一步诱导V β特异性CD 8（+）CTL的证据。
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.