Enhancement of LFA-1-mediated cell adhesion by triggering through CD2 or CD3 on T lymphocytes.
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.
van Kooyk
Y
Y
Division of Immunology, The Netherlands Cancer Institute.
van de Wiel-van Kemenade
P
P
Weder
P
P
Kuijpers
T W
TW
Figdor
C G
CG
D015703:Antigens, CD / Q000502:physiology*; D000943:Antigens, Differentiation / Q000502:physiology*; D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology*; D018801:CD2 Antigens; D017252:CD3 Complex; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology*; D002478:Cells, Cultured; D006801:Humans; D007158:Immunologic Techniques; D066298:In Vitro Techniques; D016169:Lymphocyte Function-Associated Antigen-1; D011493:Protein Kinase C / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D011971:Receptors, Immunologic / Q000502:physiology*; D016028:Receptors, Leukocyte-Adhesion / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000502:physiology*
D015703:Antigens, CD; D000943:Antigens, Differentiation; D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D011971:Receptors, Immunologic; D016028:Receptors, Leukocyte-Adhesion; D011493:Protein Kinase C