Galectin-1 induces partial TCR ζ-chain phosphorylation and antagonizes processive TCR signal transduction
Galectin-1 induces partial TCR ζ-chain phosphorylation and antagonizes processive TCR signal transduction
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DOI：
10.4049/jimmunol.165.7.3722
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发表时间：
2000-10-01
影响因子：
4.4
通讯作者：
Miceli, MC
中科院分区：
文献类型：
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作者：
Chung, CD;Patel, VP;Miceli, MC
半乳糖凝集素-1是一种内源性凝集素，具有已知的T细胞免疫调节活性，尽管半乳糖凝集素-1影响Ag特异性T细胞应答的分子基础尚未阐明。在这里，我们的特点的能力，半乳糖凝集素-1调节TCR信号和响应的T细胞与明确定义的层次结构的阈值要求的信号传导不同的功能反应。我们证明，半乳糖凝集素-1拮抗已知需要共刺激和进行性蛋白酪氨酸磷酸化的TCR应答，如IL-2产生，但允许仅需要部分TCR信号的TCR应答，如IFN-γ产生，CD 69上调和凋亡，半乳糖凝集素-1单独结合或与Ag刺激一起结合诱导TCR-ζ的部分磷酸化和抑制性pp 21 ζ的产生，半乳糖凝集素-1拮抗Ag诱导的信号和TCR/共刺激因子依赖性脂筏在TCR接触位点的聚集。我们提出半乳糖凝集素-1作为T细胞“反刺激物”发挥作用，以限制TCR接触位点处所需的蛋白质分离和脂筏重组，从而限制进行性和持续的TCR信号转导。这些发现支持TCR拮抗作用可以由抑制性pp 21 ζ-基TCR信号传导复合物的产生引起的概念。此外，他们证明TCR拮抗作用可由T细胞与肽/MHC以外的配体相互作用引起。
Galectin-1 is an endogenous lectin with known T cell immunoregulatory activity, though the molecular basis by which galectin-1 influences Ag specific T cell responses has not been elucidated. Here, we characterize the ability of galectin-1 to modulate TCR signals and responses by T cells with well defined hierarchies of threshold requirements for signaling distinct functional responses. We demonstrate that galectin-1 antagonizes TCR responses known to require costimulation and processive protein tyrosine phosphorylation, such as IL-2 production, but is permissive for TCR responses that only require partial TCR signals, such as IFN-gamma production, CD69 up-regulation, and apoptosis, Galectin-1 binding alone or together with Ag stimulation induces partial phosphorylation of TCR-zeta and the generation of inhibitory pp21 zeta, Galectin-1 antagonizes Ag induced signals and TCR/costimulator dependent lipid raft clustering at the TCR contact site. We propose that galectin-1 functions as a T cell "counterstimulator'' to limit required protein segregation and lipid raft reorganization at the TCR contact site and, thus, processive and sustained TCR signal transduction, These findings support the concept that TCR antagonism can arise from the generation of an inhibitory pp21 zeta-based TCR signaling complex. Moreover, they demonstrate that TCR antagonism can result from T cell interactions with a ligand other than peptide/MHC.