Involvement of the TCR Cbeta FG loop in thymic selection and T cell function.
Involvement of the TCR Cbeta FG loop in thymic selection and T cell function.
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TCR CBETA FG回路参与胸腺选择和T细胞功能。
DOI：
10.1084/jem.20020119
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发表时间：
2002-06-03
影响因子：
15.3
通讯作者：
Reinherz, Ellis L
中科院分区：
文献类型：
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作者：
Sasada, Tetsuro;Touma, Maki;Chang, Hsiu-Ching;Clayton, Linda K;Wang, Jia-huai;Reinherz, Ellis L
T细胞受体（TCR） Cβ和Cα外畴的不对称配置产生了一个腔，其侧壁由刚性的Cβ FG环形成。为了研究这种保守结构的意义，我们利用N15 CTL的TCR β亚基产生了环缺失（βΔFG）和βwt转基因（tg）小鼠。N15βwt和N15βΔFG H-2b动物在S期胸腺细胞数量相当，并通过CD4 - CD8 -双阴性（DN）细胞室表现出发育进展。N15βΔFG促进重组酶激活基因(RAG)-2−/−小鼠从DN到CD4+8+双阳性（DP）胸腺细胞的转变，表明tcr前功能仍然存在。N15βΔFG动物拥有约两倍的CD8+单阳性（SP）胸腺细胞和淋巴结T细胞，与增强的阳性选择一致。由于在N15βΔFG小鼠中观察到的Vα库的改变可能混淆了缺失的作用，我们将N15αβ TCR tg RAG-2−/−与N15βΔFG tg RAG-2−/−H-2b小鼠杂交，生成N15αβ RAG-2−/−和N15αβ。βΔFG rag2−/−littermates。N15αβ。βΔFG由于负选择减少，rag2 - / -小鼠的胸腺细胞DP增加了8 - 10倍，这可以通过减少组成型和同源肽诱导的凋亡来证明。与N15αβ相比，N15αβ。βΔFG T细胞对同源抗原和弱激动剂反应差。因此，Cβ FG环促进胸腺细胞的负选择和T细胞的激活。
The asymmetric disposition of T cell receptor (TCR) Cβ and Cα ectodomains creates a cavity with a side-wall formed by the rigid Cβ FG loop. To investigate the significance of this conserved structure, we generated loop deletion (βΔFG) and βwt transgenic (tg) mice using the TCR β subunit of the N15 CTL. N15βwt and N15βΔFG H-2b animals have comparable numbers of thymocytes in S phase and manifest developmental progression through the CD4−CD8− double-negative (DN) compartment. N15βΔFG facilitates transition from DN to CD4+8+ double-positive (DP) thymocytes in recombinase activating gene (RAG)-2−/− mice, showing that pre-TCR function remains. N15βΔFG animals possess ∼twofold more CD8+ single-positive (SP) thymocytes and lymph node T cells, consistent with enhanced positive selection. As an altered Vα repertoire observed in N15βΔFG mice may confound the deletion's effect, we crossed N15αβ TCR tg RAG-2−/− with N15βΔFG tg RAG-2−/− H-2b mice to generate N15αβ RAG-2−/− and N15αβ.βΔFG RAG-2−/− littermates. N15αβ.βΔFG RAG-2−/− mice show an 8–10-fold increase in DP thymocytes due to reduced negative selection, as evidenced by diminished constitutive and cognate peptide-induced apoptosis. Compared with N15αβ, N15αβ.βΔFG T cells respond poorly to cognate antigens and weak agonists. Thus, the Cβ FG loop facilitates negative selection of thymocytes and activation of T cells.