The constitutive tyrosine phosphorylation of CD3ζresults from TCR-MHC interactions that are independent of thymic selection
The constitutive tyrosine phosphorylation of CD3ζresults from TCR-MHC interactions that are independent of thymic selection
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DOI：
10.4049/jimmunol.178.7.4120
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发表时间：
2007-04-01
影响因子：
4.4
通讯作者：
van Oers, Nicolai S. C.
中科院分区：
文献类型：
--
作者：
Becker, Amy M.;DeFord-Watts, Laura M.;van Oers, Nicolai S. C.
当从胸腺细胞和外周T细胞中分离出来时，TCR复合物含有一种组成型酪氨酸磷酸化的CD3分子，称为p21。先前的研究表明，CD3的组成性磷酸化是由TCR与胸腺和外周发生的MHC分子相互作用引起的。为了确定选择环境对这种组成性磷酸化的贡献，我们分析了几种不同的I类和ii类限制性tcr转基因小鼠的CD3，其中胸腺细胞发育发生在选择或非选择的MHC环境中。在此，我们报告了在非选择性肽- mhc条件下发育的胸腺细胞中存在组成性磷酸化的CD3 zeta （p21）。这些发现有力地支持了TCR在曲目选择之前对MHC分子具有固有亲和力的模型。TCR刺激前后TCR复合物的生化分析表明，组成磷酸化的CD3亚基不参与新生TCR信号。这些发现可能对T细胞在正常和自身免疫情况下自我mhc识别过程中的功能具有重要意义。
The TCR complex, when isolated from thymocytes and peripheral T cells, contains a constitutively tyrosine-phosphorylated CD3 molecule termed p21. Previous investigations have shown that the constitutive phosphorylation of CD3 results from TCR interactions with MHC molecules occurring in both the thymus and the periphery. To determine what contribution the selection environment had on this constitutive phosphorylation, we analyzed CD3 from several distinct class I- and II-restricted TCRtransgenic mice where thymocyte development occurred in either a selecting or a nonselecting MHC environment. Herein, we report that constitutively phosphorylated CD3 zeta (p21) was present in thymocytes that developed under nonselecting peptide-MHC conditions. These findings strongly support the model that the TCR has an inherent avidity for MHC molecules before repertoire selection. Biochemical analyses of the TCR complex before and after TCR stimulation suggested that the constitutively phosphorylated CD3 subunit did not contribute to de novo TCR signals. These findings may have important implications for T cell functions during self-MHC recognition under normal and autoimmune circumstances.