Prevalent role of TCR α-chain in the selection of the preimmune repertoire specific for a human tumor-associated self-antigen
Prevalent role of TCR α-chain in the selection of the preimmune repertoire specific for a human tumor-associated self-antigen
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DOI：
10.4049/jimmunol.170.10.5103
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发表时间：
2003-05-15
影响因子：
4.4
通讯作者：
Valmori, D
中科院分区：
文献类型：
--
作者：
Dietrich, PY;Le Gal, FA;Valmori, D
T淋巴细胞识别pMHC复合物的特异性是由TCR α链和β链的V区决定的。最近的实验证据表明，ag特异性TCR库可能表现出更多的vpha -而不是vβ -限制使用。然而，在对Ag的免疫应答过程中，Valpha的使用是否会被缩小，或者相反，在TCR库选择的早期阶段，是否已经定义了有限的Valpha使用，目前仍未得到研究。在这里，我们分析了体外特异性检测的单循环初始T细胞的V和CDR3 TCR区域，并用HLA-A2/melan-A肽多聚体分离。与之前在黑色素- a特异性ag -experience T细胞中观察到的类似，我们发现相对广泛的Vbeta使用，但优先使用vpha 2.1。在单个CD8(+) A2/melan-A多时间（+）胸腺细胞中也发现限制Valpha 2.1的使用，表明Valpha限制性选择发生在胸腺中。然而，Valpha 2.1的使用与Ag识别的功能贪婪度无关。因此，pMHC复合物与选定的Valpha-链的相互作用有助于建立广泛的Ag特异性，正如A2/melan-A多聚体优先结合到携带Valpha 2.1的TCR上所强调的那样，而功能结果则是pMHC复合物与TCR之间其他相互作用的结果。
The specificity of recognition of pMHC complexes by T lymphocytes is determined by the V regions of the TCR alpha- and beta-chains. Recent experimental evidence has suggested that Ag-specific TCR repertoires may exhibit a more Valpha- than Vbeta-restricted usage. Whether Valpha usage is narrowed during immune responses to Ag or if, on the contrary, restricted Valpha usage is already defined at the early stages of TCR repertoire selection, however, has remained unexplored. Here, we analyzed V and CDR3 TCR regions of single circulating naive T cells specifically detected ex vivo and isolated with HLA-A2/melan-A peptide multimers. Similarly to what was previously observed for melan-A-specific Ag-experienced T cells, we found a relatively wide Vbeta usage, but a preferential Valpha 2.1 usage. Restricted Valpha 2.1 usage was also found among single CD8(+) A2/melan-A multimer(+) thymocytes, indicating that Valpha-restricted selection takes place in the thymus. Valpha 2.1 usage, however, was independent from functional avidity of Ag recognition. Thus, interaction of the pMHC complex with selected Valpha-chains contributes to set the broad Ag specificity, as underlined by preferential binding of A2/melan-A multimers to Valpha 2.1-bearing TCRs, whereas functional outcomes result from the sum of these with other interactions between pMHC complex and TCR.