Rosshart Stephan, Hofmann Maike, Schweier Oliver, Pfaff Anne-Kathrin, Yoshimoto Keiko, Takeuchi Tsutomu, Molnar Eszter, Schamel Wolfgang W, Pircher Hanspeter
Department of Immunology, Institute of Medical Microbiology and Hygiene, University of Freiburg, Germany.
Eur J Immunol. 2008 Dec;38(12):3354-64. doi: 10.1002/eji.200838690.
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 Y(7)F-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.
杀伤细胞凝集素样受体G1（KLRG1）是一种抑制性受体，在人和小鼠的记忆T细胞和自然杀伤细胞中表达。它经常被用作细胞分化标志物，钙黏蛋白家族成员是KLRG1的配体。本研究为小鼠KLRG1与E-钙黏蛋白的相互作用提供了新的见解。首先，我们证明KLRG1和CD3/TCR以空间连接的方式共同参与抑制作用，这与KLRG1自身结合传递抑制信号的观点相悖。其次，对携带Y(7)F突变型KLRG1分子的T细胞进行实验，该分子在单个免疫受体酪氨酸抑制基序中将酪氨酸残基替换为苯丙氨酸，结果表明KLRG1(+) T细胞与表达E-钙黏蛋白的靶细胞之间相互作用增加，在一定程度上抵消了KLRG1的抑制活性。第三，我们证明在KLRG1报告细胞试验中，E-钙黏蛋白第一或第二胞外结构域的缺失消除了反应性。最后，我们有一个有趣的发现，即除了先前描述的单体和二聚体分子外，KLRG1在T细胞中还形成多聚体蛋白复合物。
