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Intercellular adhesion molecule-1 (ICAM-1, CD54) is a ligand for the integrins lymphocyte function associated-1 (LFA-1, CD11a/CD18) and complement receptor-3 (Mac-1, CD11b/CD18) making it an important participant in many immune and inflammatory processes. Modified recombinant soluble ICAM-1 formed dimers. This result indicated that the ectodomain of ICAM-1 contains homophilic interaction sites. Soluble ICAM-1 dimers bind to solid-phase purified LFA-1 with high avidity (dissociation constant [Kd] = 8 nM) in contrast to soluble ICAM-1 monomers whose binding was not measurable. Cell surface ICAM-1 was found to be dimeric based on two distinct criteria. First, a monoclonal antibody specific for monomeric soluble ICAM-1, CA7, binds normal ICAM-1 poorly at the cell surface; this antibody, however, binds strongly to two mutant forms of ICAM-1 when expressed at the cell surface, thus identifying elements required for dimer formation. Second, chemical cross-linking of cell surface ICAM-1 on transfected cells and tumor necrosis factor-activated endothelial cells results in conversion of a portion of ICAM-1 to a covalent dimer. Cell surface ICAM-1 dimers are more potent ligands for LFA-1-dependent adhesion than ICAM-1 monomers. While many extracellular matrix-associated ligands of integrins are multimeric, this is the first evidence of specific, functionally important homodimerization of a cell surface integrin ligand.

Original publication

DOI

10.1084/jem.182.5.1231

Type

Journal article

Journal

The Journal of experimental medicine

Publication Date

11/1995

Volume

182

Pages

1231 - 1241

Addresses

Center for Immunology, Washington University School of Medicine, St. Louis, Missouri, USA.

Keywords

Endothelium, Vascular, B-Lymphocytes, Cells, Cultured, Cell Line, Transformed, Animals, Cercopithecus aethiops, Humans, Intercellular Adhesion Molecule-1, Lymphocyte Function-Associated Antigen-1, Recombinant Proteins, Antibodies, Monoclonal, Cell Adhesion, Protein Conformation, Protein Binding, Solubility, Cricetinae