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Molecular cloning of ICAM-3, a third ligand for LFA-1, constitutively expressed on resting leukocytes

Abstract

THE co-ordinated function of effector and accessory cells in the immune system is assisted by adhesion molecules on the cell surface that stabilize interactions between different cell types1. Leukocyte function-associated antigen 1 (LFA-1) is expressed on the surface of all white blood cells2 and is a receptor for intercellular adhesion molecules (ICAM) 1 and 2 (ref. 3) which are members of the immunoglobulin superfamily4–6. The interaction of LFA-1 with ICAMs 1 and 2 provides essential accessory adhesion signals in many immune interactions, including those between T and B lymphocytes7 and cytotoxic T cells and their targets8,9. In addition, both ICAMs are expressed at low levels on resting vascular endothelium10; 1C AM-1 is strongly upregulated by cytokine stimulation and plays a key role in the arrest of leukocytes in blood vessels at sites of inflammation and injury. Recent work has indicated that resting leukocytes express a third ligand, ICAM-3, for LFA-1 (refs 11,12). ICAM-3 is potentially the most important ligand for LFA-1 in the initiation of the immune response because the expression of ICAM-1 on resting leukocytes is low. We report the expression cloning of a complementary DNA, pICAM-3, encoding a protein constitutively expressed on all leukocytes, which binds LFA-1. ICAM-3 is closely related to ICAM-1, consists of five immunoglobulin domains, and binds LFA-1 through its two N-terminal domains.

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Fawcett, J., Holness, C., Needham, L. et al. Molecular cloning of ICAM-3, a third ligand for LFA-1, constitutively expressed on resting leukocytes. Nature 360, 481–484 (1992). https://doi.org/10.1038/360481a0

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