Interaction of KLRG1 with E-cadherin: New functional and structural insights
Interaction of KLRG1 with E-cadherin: New functional and structural insights
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DOI：
10.1002/eji.200838690
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发表时间：
2008-12-01
影响因子：
5.4
通讯作者：
Pircher, Hanspeter
中科院分区：
文献类型：
--
作者：
Rosshart, Stephan;Hofmann, Maike;Pircher, Hanspeter
杀伤细胞凝集素样受体G1（KLRG 1）是由人和小鼠的记忆T细胞和NK细胞表达的抑制性受体。它经常被用作细胞分化标志物，钙粘蛋白家族的成员是KLRG 1的配体。本研究为小鼠KLRG 1与E-cadherin的相互作用提供了新的见解。首先，我们证明了KLRG 1和CD 3/TCR以空间连接的方式共同参与是抑制所需的，这与KLRG 1连接本身传递抑制信号的观点相反。其次，用携带Y 7 F突变KLRG 1分子的T细胞进行的实验表明，KLRG 1的抑制活性在一定程度上被KLRG 1（+）T细胞与表达E-钙粘蛋白的靶细胞的相互作用增强所抵消。第三，我们证明，删除的第一或第二个外部结构域的E-钙粘蛋白废除KLRG 1报告细胞检测反应。最后，我们做了有趣的观察，KLRG 1形成多聚体蛋白复合物在T细胞中除了以前描述的单和二聚体分子。
The killer cell lectin-like receptor G1 (KLRG1) is an inhibitory receptor expressed by memory T cells and NK cells in man and mice. It is frequently used as a cell differentiation marker and members of the cadherin family are ligands for KLRG1. The present study provides new insights into the interaction of mouse KLRG1 with E-cadherin. Firstly, we demonstrate that co-engagement of KLRG1 and CD3/TCR in a spatially linked manner was required for inhibition arguing against the notion that KLRG1-ligation per se transmits inhibitory signals. Secondly, experiments with T cells carrying Y7F-mutant KLRG1 molecules with a replacement of the tyrosine residue to phenylalanine in the single ITIM indicated that the inhibitory activity of KLRG1 is counteracted to some degree by increased interaction of KLRG1(+) T cells with E-cadherin expressing target cells. Thirdly, we demonstrate that deletion of the first or the second external domain of E-cadherin abolished reactivity in KLRG1-reporter cell assays. Finally, we made the intriguing observation that KLRG1 formed multimeric protein complexes in T cells in addition to the previously described mono- and dimeric molecules.