Enhancement of LFA-1-mediated cell adhesion by triggering through CD2 or CD3 on T lymphocytes

THE lymphocyte function-associated molecule LFA-1 (CD 11 a/ CD 18) plays a key part in lymphocyte adhesion1,2. Lymphocytes do not adhere spontaneously; activation of protein kinase C (PKC)3 by phorbol esters, however, gives rise to strong LFA-1-dependent adhesion4, 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 lymphocytes5–8 are involved in the activation of LFA-1. The stimulation of these molecules, which causes activation of PKC9,10, 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.