Regulatory properties of LFA-1 alpha and beta chains in human T-lymphocyte activation.
Lymphocyte function-associated antigen-1 (LFA-1) is a heterodimer composed of an alpha and beta chain that is expressed on the surface of most leukocytes and is an essential molecule for adhesion reactions between cells participating in the immune response. A putative ligand for LFA-1 is the intercellular adhesion molecule ICAM-1 (refs 3-5). Leukocyte adhesion abnormality is found in patients with LFA-1 deficiency. It is not clear whether binding of ligand to the LFA-1 molecule merely spatially orientates cells towards each other or can also induce signals that regulate cell activation and differentiation. We have recently developed a T-cell proliferation assay which uses immobilized anti-CD3 monoclonal antibodies as stimulant and is independent of LFA-1-mediated cellular adhesion. As there is no interference by anti-LFA-1 monoclonal antibodies with the adhesion-dependent activation steps, this T-cell activation system allows us to investigate whether transmembrane signals are induced by binding of ligand to LFA-1 on T cells. Our data indicate that binding of ligand to LFA-1 results in the transduction of regulatory signal across the plasma membrane, rather like other molecules (CD2, CD4, CD8) (refs 8-11) with signal-modifying properties involved in the adhesion of T cells to target/stimulator cells. Indeed, adhesion molecules might generally be important in signal transduction, even in cells not belonging to the immune system.
van Noesel
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C
Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, University of Amsterdam, The Netherlands.
Miedema
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Brouwer
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de Rie
M A
MA
Aarden
L A
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van Lier
R A
RA
D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D000954:Antigens, Surface / Q000172:deficiency / Q000502:physiology*; D017252:CD3 Complex; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000276:immunology; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D017252:CD3 Complex; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell