Identification of a highly cross-reactive CD8+ T cell repertoire that recognizes an HEV peptide and an apoptotic epitope
Identification of a highly cross-reactive CD8+ T cell repertoire that recognizes an HEV peptide and an apoptotic epitope
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鉴定可识别 HEV 肽和凋亡表位的高度交叉反应性 CD8 T 细胞库
DOI：
10.1055/s-0036-1597501
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发表时间：
2016
期刊：
影响因子：
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通讯作者：
S Zhang
中科院分区：
文献类型：
--
作者：
CF Soon;AA Markova;HH Wedemeyer;MP Manns;M Cornberg;S Zhang
结果：ICS检测的4例未暴露个体中有3例检测到hev特异性CD8+ T细胞。在一个供体中，我们检测到HEV 9聚肽与凋亡表位MYH9-478之间存在强烈的交叉反应。用HEV肽体外刺激14天后，高达25%的CD8+ T细胞MYH9-478右旋聚体阳性，在HEV肽再刺激后产生细胞因子。有趣的是，序列分析显示TCR具有高度的寡克隆库，最多具有两种T细胞克隆型。所有克隆在TCR β链上都显示了一个不寻常的CDR3基序，具有多个甘氨酸，这可能有助于解释TCR与两个非常不同的表位相互作用的灵活性（9个同源性中有2个）。结论：我们的研究为HEV血清阴性个体的HEV特异性CD8+ T细胞交叉反应提供了证据。与凋亡表位的交叉反应性赋予这些T细胞自身炎症的潜能。TCR中不寻常的富含甘氨酸的区域可能是高度交叉反应的T细胞的特征和诊断特征。
Results: Notable HEV-specific CD8+ T cell were detected in 3 out of 4 unexposed individuals tested by ICS. In one donor, we detected strong cross-reactivity between an HEV 9mer peptide and apoptotic epitope MYH9–478. After 14 days in-vitro stimulation with the HEV peptide, up to 25% of CD8+ T cells were MYH9–478 dextramer positive, which produced cytokine upon HEV peptide restimulation. Interestingly, sequence analysis of TCR showed a highly oligoclonal repertoire, with a maximum of two T cell clonotypes. All clones showed an unusual CDR3 motif in the TCR β chain with multiple glycines, which may help to explain the flexibility of the TCR to interact with two very different epitopes (2 out of 9 aa homology).Conclusion: Our study provides evidence for cross-reactive HEV-specific CD8+ T cells in HEV seronegative individuals. The cross-reactivity with apoptotic epitopes gives these T cells autoinflammatory potential. The unusual glycine-rich region in TCR may be a feature of highly cross-reactive T cells and of diagnostic characteristic.