I domain of beta 2 integrin lymphocyte function-associated antigen-1 contains a binding site for ligand intercellular adhesion molecule-1.
Lymphocyte function-associated antigen-1 (LFA-1) is a beta 2 integrin that participates in a broad range of leukocyte functions through binding to its ligand intercellular adhesion molecule-1 (ICAM-1). The location of the ICAM-1 binding site on LFA-1 is not known. A approximately 200-amino acid "inserted" or "I" domain, which is part of the beta 2 integrin alpha subunit, is homologous to the "A" domains found in the adhesive protein von Willebrand factor and in a number of other proteins. In von Willebrand factor, the A domains are involved in ligand binding, but their function in the other proteins is still unclear. In this report, we show that the LFA-1 I domain contains a binding site for ICAM-1, which can be expressed as an isolated functional unit. The I domain contains the epitopes for 18 out of 20 anti-LFA-1 monoclonal antibodies, many of which interfere with the interaction between LFA-1 and ICAM-1. The I domain binds directly to purified recombinant ICAM-1 and also inhibits LFA-1-dependent T cell adhesion to ICAM-1. This report establishes the I domain as an ICAM-1 binding region in LFA-1 and the first ligand binding site to be identified in a beta 2 integrin.
Randi
A M
AM
Leukocyte Adhesion Laboratory, Imperial Cancer Research Fund, London, United Kingdom.
Hogg
N
N
D000911:Antibodies, Monoclonal; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D011485:Protein Binding; D011961:Receptors, Fc / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D011961:Receptors, Fc; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1