Cutting edge: Molecular analysis of the negative regulatory function of lymphocyte activation gene-3
Cutting edge: Molecular analysis of the negative regulatory function of lymphocyte activation gene-3
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DOI：
10.4049/jimmunol.169.10.5392
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发表时间：
2002-11-15
影响因子：
4.4
通讯作者：
Vignaw, DAA
中科院分区：
文献类型：
--
作者：
Workman, CJ;Dugger, KJ;Vignaw, DAA
淋巴细胞活化基因(LAG)-3(CD223)是一种CD4相关的活化诱导细胞表面分子，与MHC-II类分子高亲和力结合，负向调节T细胞的增殖和动态平衡。在这项研究中，我们发现LAG-3通过其胞浆结构域抑制依赖于CD4的T细胞的功能，但不抑制非依赖于CD4的T细胞的功能。虽然与MHC II类分子的高亲和力相互作用对于Lag-3的功能是必不可少的，但无尾Lag-3并不与CD4竞争配体结合。保守的“KIEELE”基序中的单一赖氨酸残基(K468)对于与下游信号分子的相互作用是必不可少的。这些数据为深入了解这种重要的T细胞调节分子的作用机制提供了依据。
Lymphocyte activation gene (LAG)-3 (CD223) is a CD4-related activation-induced cell surface molecule that binds to MHC class II molecules with high affinity and negatively regulates T cell expansion and homeostasis. In this study, we show that LAG-3 inhibits CD4-dependent, but not CD4-independent, T cell function via its cytoplasmic domain. Although high affinity interaction with MHC class II molecules is essential for LAG-3 function, tailless LAG-3 does not compete with CD4 for ligand binding. A single lysine residue (K468) within a conserved "KIEELE" motif is essential for interaction with downstream signaling molecules. These data provide insight into the mechanism of action of this important T cell regulatory molecule.