Department of Pharmaceutical Biology, Faculty of Pharmacy, University of Ljubljana, Ljubljana, Slovenia.
IUBMB Life. 2011 Sep;63(9):686-93. doi: 10.1002/iub.505. Epub 2011 Jul 27.
The adhesion molecule lymphocyte function-associated antigen (LFA)-1 plays a key role in immune surveillance and response. Its conformation is spatially and temporally regulated, enabling adhesion and deadhesion during T-cell migration. LFA-1 adhesion to its major ligand intercellular adhesion molecule 1 is controlled by adaptor proteins which bind the cytoplasmic tail of the β (2) subunit. Cathepsin X, a cysteine carboxypeptidase, promotes T-cell migration and morphological changes by cleaving the β (2) cytoplasmic tail of LFA-1. In this way, it modulates the affinity of LFA-1 for structural adaptors talin-1 and α-actinin-1 and enables the stepwise transition between intermediate and high-affinity conformations of LFA-1, an event that is necessary for effective T-cell function. Cathepsin X regulation that would allow precise modulation of LFA-1 affinity has a great potential for anti-LFA-1 therapy.
黏附分子淋巴细胞功能相关抗原（LFA）-1 在免疫监视和反应中起着关键作用。其构象在空间和时间上受到调节，使 T 细胞迁移过程中发生黏附和脱黏附。LFA-1 与其主要配体细胞间黏附分子 1 的黏附受衔接蛋白的控制，后者结合β（2）亚基的胞质尾。组织蛋白酶 X 是一种半胱氨酸羧肽酶，通过切割 LFA-1 的β（2）胞质尾来促进 T 细胞迁移和形态变化。通过这种方式，它调节 LFA-1 与结构衔接蛋白 talin-1 和 α-辅肌动蛋白-1 的亲和力，并使 LFA-1 从中间亲和力构象向高亲和力构象的逐步转变成为有效 T 细胞功能所必需的。组织蛋白酶 X 的调节可以精确地调节 LFA-1 的亲和力，这对于抗 LFA-1 治疗具有巨大的潜力。
