The CD3 zeta subunit contains a phosphoinositide-binding motif that is required for the stable accumulation of TCR-CD3 complex at the immunological synapse.
The CD3 zeta subunit contains a phosphoinositide-binding motif that is required for the stable accumulation of TCR-CD3 complex at the immunological synapse.
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DOI：
10.4049/jimmunol.1002721
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发表时间：
2011-06-15
期刊：
影响因子：
--
通讯作者：
van Oers NS
中科院分区：
文献类型：
--
作者：
DeFord-Watts LM;Dougall DS;Belkaya S;Johnson BA;Eitson JL;Roybal KT;Barylko B;Albanesi JP;Wülfing C;van Oers NS
T细胞活化涉及TCR介导的信号级联，其由位于CD 3链的胞质尾内的三个不同的细胞内信号传导基序调节。虽然所有的CD 3亚基都具有至少一个ITAM，但CD 3 ε亚基还含有富含脯氨酸的序列（PRS）和富含碱性的片段（BRS）。CD 3 ε BRS复合物选择磷酸肌醇，这是TCR正常细胞表面表达所需的相互作用。CD 3 β的胞质结构域还含有几簇精氨酸和赖氨酸残基。在此，我们报道了这些碱性氨基酸使CD 3 γ能够以高亲和力复合磷酸肌醇PtdIns（3）P、PtdIns（4）P、PtdIns（5）P、PtdIns（3，5）P2和PtdIns（3，4，5）P3。早期TCR信号通路不受CD 3+磷酸肌醇结合功能靶向丧失的影响。相反，CD 3 γ的磷酸肌醇结合功能的消除显著损害了这种不变链在T细胞-抗原呈递细胞相互作用期间在免疫突触处稳定积累的能力。没有其磷酸肌醇结合功能，CD 3 β在T细胞活化后集中在细胞内结构中。这些发现证明了CD 3配体-磷酸肌醇相互作用在支持T细胞活化中的新功能作用。
T cell activation involves a cascade of TCR-mediated signals that are regulated by three distinct intracellular signaling motifs located within the cytoplasmic tails of the CD3 chains. While all the CD3 subunits possess at least one ITAM, CD3 ε subunit also contains a proline-rich sequence (PRS) and a basic-rich stretch (BRS). The CD3 ε BRS complexes selected phosphoinositides, interactions that are required for normal cell surface expression of the TCR. The cytoplasmic domain of CD3 ζ also contains several clusters of arginine and lysine residues. Herein, we report that these basic amino acids enable CD3 ζ to complex the phosphoinositides PtdIns(3)P, PtdIns(4)P, PtdIns(5)P, PtdIns(3,5)P2, and PtdIns(3,4,5)P3 with high affinity. Early TCR signaling pathways were unaffected by the targeted loss of the phosphoinositide-binding functions of CD3 ζ. Instead, the elimination of the phosphoinositide-binding function of CD3 ζ significantly impaired the ability of this invariant chain to stably accumulate at the immunological synapse during T cell-antigen presenting cell interactions. Without its phosphoinositide-binding functions, CD3 ζ was concentrated in intracellular structures following T cell activation. Such findings demonstrate a novel functional role for CD3 ζ BRS-phosphoinositide interactions in supporting T cell activation.
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影响因子：
64.5
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