Role of ligands in the activation of LFA-1.
Lymphocyte function-associated-antigen-1 (LFA-1) is able to bind selectively to its ligands intercellular adhesion molecules 1 and 3 (ICAM-1 and ICAM-3), suggesting that LFA-1 can exist in distinct ligand-specific binding states. In the case of ICAM-1, apart from ligand itself and the recently cloned molecule cytohesin-1, the natural physiological regulators of LFA-1-mediated binding to ICAM-1 are unknown. We have investigated the role of ligands (ICAM-1 and ICAM-3) in LFA-1 activation by using ICAM-blocking monoclonal antibodies and a fixation protocol for "freezing" LFA-1 on the surface of cells after prior exposure to ICAM-1 and ICAM-3. These studies not only confirm that LFA-1 exists in distinct ICAM-specific activation states, but also demonstrate that ICAM-1 plays a role in the activation of LFA-1 binding to ICAM-3.
Buckley
C D
CD
Imperial Cancer Research Fund, Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, GB.
Ferguson
E D
ED
Littler
A J
AJ
Bossy
D
D
Simmons
D L
DL
D015703:Antigens, CD; D000943:Antigens, Differentiation; D002448:Cell Adhesion / Q000187:drug effects / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000502:physiology*; D005404:Fixatives; D005557:Formaldehyde; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology*; D004915:Leukemia, Erythroblastic, Acute; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D011108:Polymers; D011485:Protein Binding / Q000187:drug effects / Q000276:immunology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; D005404:Fixatives; C483616:ICAM3 protein, human; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D011108:Polymers; D018799:Intercellular Adhesion Molecule-1; D005557:Formaldehyde; C003043:paraform