Ligand intercellular adhesion molecule 1 has a necessary role in activation of integrin lymphocyte function-associated molecule 1.
The signaling that causes the leukocyte integrin lymphocyte function-associated molecule (LFA-1) to bind firmly to its ligand intercellular adhesion molecule 1 (ICAM-1) is transduced indirectly through other T-cell receptors and is termed inside-out signaling. We show here that the high-affinity state of LFA-1 is characterized by expression of the LFA-1 epitope detected by monoclonal antibody 24. This epitope is expressed not in response to the initial agonist-mediated signal but when LFA-1 binds to ICAM-1, indicating that ligand binding induces an alteration in LFA-1. As would be predicted, the monoclonal antibody 24 epitope is confined to the LFA-1, which is located at the site of contact between T cells and ICAM-1-expressing transfectants. When a fixation protocol for "freezing" receptors is used, only T cells that are fixed after prior exposure to ICAM-1 bind firmly to ICAM-1 a second time. This suggests that, in addition to the inside-out signaling, a previously unrecognized requirement for full activation of the leukocyte integrin LFA-1 is the initial interaction with its ligand ICAM-1. Thus, activation of LFA-1 is in part achieved by an induced fit imposed from without by interaction with ligand.
Cabañas
C
C
Imperial Cancer Research Fund, London, United Kingdom.
Hogg
N
N
D000818:Animals; D000911:Antibodies, Monoclonal; D015703:Antigens, CD / Q000378:metabolism; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D004533:Egtazic Acid / Q000494:pharmacology; D000939:Epitopes / Q000032:analysis / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000378:metabolism; D007074:Immunoglobulin G / Q000378:metabolism; D018799:Intercellular Adhesion Molecule-1; D007700:Kinetics; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000378:metabolism*; D008274:Magnesium / Q000494:pharmacology; D008345:Manganese / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D014162:Transfection
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D000939:Epitopes; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D011993:Recombinant Fusion Proteins; D018799:Intercellular Adhesion Molecule-1; D008345:Manganese; D004533:Egtazic Acid; D008274:Magnesium