The TCR Cβ FG loop regulates αβ T cell development
The TCR Cβ FG loop regulates αβ T cell development
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DOI：
10.4049/jimmunol.176.11.6812
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发表时间：
2006-06-01
影响因子：
4.4
通讯作者：
Reinherz, Ellis L.
中科院分区：
文献类型：
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作者：
Touma, Maki;Chang, Hsiu-Ching;Reinherz, Ellis L.
TCRP链的恒定结构域包含一个异常细长的、暴露在溶剂中的FG环。这种结构元件形成了α-βTCR空腔的一个组成部分，CD3-epsilon-伽马可以与其毗邻，以促进Ag特异的信号转导。与这一概念一致，在本研究中，我们表明表达FG环缺失链(ββFG)的N15αβTCR转染体比那些在TCR交联时含有野生型β链(βwt)的转染体刺激更少的酪氨酸蛋白磷酸化。此外，免疫共沉淀研究表明，在含有βDelta FG变体的TCR复合体中，CD3 epsilonγ异二聚体与β链之间的关联减弱。为了进一步研究CβFG环在发育过程中的生物学作用，我们用转BβFg基因的C57BL/6(B6)小鼠的骨髓细胞竞争性地重建了Ly5同源基因或RAG-2(-/-)小鼠的胸腺。βWt和βDelta FG前体细胞都能产生代表所有成熟阶段的胸腺细胞。然而，在随后的发育过程中，表达β-Delta Fg的胸腺细胞占主导地位，导致过量表达β-Delta Fg的外周T细胞，在TCR刺激下增殖和细胞因子产生能力降低。总而言之，我们的结果表明，独特的CβFG环附件主要通过选择过程控制αβT细胞的发育。
The TCRP chain constant domain contains an unusually elongated, solvent-exposed FG loop. This structural element forms one component of an alpha beta TCR cavity against which CD3 epsilon gamma may abut to facilitate Ag-specific signaling. Consistent with this notion, in the present study we show that N15 alpha beta TCR transfectants expressing a FG loop-deleted chain (beta Delta FG) stimulate less tyrosine protein phosphorylation than those bearing a wild-type beta-chain (beta wt) upon TCR cross-linking. Furthermore, coimmunoprecipitation studies suggest a weakened association between the CD3 epsilon gamma heterodimer and the beta-chain in TCR complexes containing the beta Delta FG variant. To further investigate the biologic role of the C beta FG loop in development, we competitively reconstituted the thymus of Ly5 congenic or RAG-2(-/-) mice using bone marrow cells from beta wt or beta Delta FG transgenic C57BL/6 (B6) mice. Both beta wt and beta Delta FG precursor cells generate thymocytes representative of all maturational stages. However, beta Delta FG-expressi'ng thymocytes dominate during subsequent development, resulting in an excess of beta Delta FG-expressing peripheral T cells with reduced proliferative and cytokine production abilities upon TCR stimulation. Collectively, our results show that the unique C beta FG loop appendage primarily controls alpha beta T cell development through selection processes.