van Kooyk Y, van de Wiel-van Kemenade P, Weder P, Kuijpers T W, Figdor C G
Division of Immunology, The Netherlands Cancer Institute.
Nature. 1989 Dec 14;342(6251):811-3. doi: 10.1038/342811a0.
The lymphocyte function-associated molecule LFA-1 (CD11a/CD18) plays a key part in lymphocyte adhesion. Lymphocytes do not adhere spontaneously; activation of protein kinase C (PKC) by phorbol esters, however, gives rise to strong LFA-1-dependent adhesion, indicating that activation of LFA-1 is required to induce cell adhesion. We have now investigated whether the functionally important CD2 and CD3 surface structures on T lymphocytes are involved in the activation of LFA-1. The stimulation of these molecules, which causes activation of PKC, strongly promoted LFA-1-dependent adhesion. Furthermore, we demonstrate by using cells from an LFA-1-deficient patient that this enhanced lymphocyte adhesion is caused by activation of the LFA-1 molecule and not by activation of its ligands. LFA-1 was persistently activated by triggering through CD2 but only transiently by triggering through CD3. We postulate that CD2 and CD3 can differentially regulate the affinity of LFA-1 for its ligands by modulating its molecular conformation through PKC-dependent mechanisms.
淋巴细胞功能相关分子LFA-1（CD11a/CD18）在淋巴细胞黏附中起关键作用。淋巴细胞不会自发黏附；然而，佛波酯激活蛋白激酶C（PKC）会引发强烈的依赖LFA-1的黏附，这表明LFA-1的激活是诱导细胞黏附所必需的。我们现在研究了T淋巴细胞上功能重要的CD2和CD3表面结构是否参与LFA-1的激活。这些分子的刺激会导致PKC激活，强烈促进依赖LFA-1的黏附。此外，我们通过使用一名LFA-1缺陷患者的细胞证明，这种增强的淋巴细胞黏附是由LFA-1分子的激活而非其配体的激活引起的。通过CD2触发可使LFA-1持续激活，但通过CD3触发仅使其短暂激活。我们推测，CD2和CD3可通过PKC依赖机制调节LFA-1的分子构象，从而差异调节LFA-1对其配体的亲和力。
