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The leukocyte adhesion molecule LFA-1 mediates a wide range of lymphocyte, monocyte, natural killer cell, and granulocyte interactions with other cells in immunity and inflammation. LFA-1 (CD11a/CD18) is a receptor for intercellular adhesion molecule 1 (ICAM-1, CD54), a surface molecule which is constitutively expressed on some tissues and induced on other in inflammation. Induction of ICAM-1 on epithelial cells, endothelial cells and fibroblasts mediates LFA-1-dependent adhesion of lymphocytes. Several lines of evidence have suggested the existence of a second LFA-1 ligand: homotypic adhesion of one cell line was inhibited by a monoclonal antibody to LFA-1, but not by one to ICAM-1; there exists an LFA-1-dependent, ICAM-1-independent pathway of adhesion to endothelial cells; and also, there are some types of target cells in which LFA-1-dependent T-lymphocyte adhesion and lysis are independent of ICAM-1. We have cloned this second ligand, designated ICAM-2, using a novel method for identifying ligands of adhesion molecules. ICAM-2 is an integral membrane protein with two immunoglobulin-like domains, whereas ICAM-1 has five. Remarkably, ICAM-2 is much more closely related to the two most N-terminal domains of ICAM-1 (34% identity) than either ICAM-1 or ICAM-2 is to other members of the immunoglobulin superfamily, demonstrating the existence of a subfamily of immunoglobulin-like ligands that bind the same integrin receptor.

Original publication

DOI

10.1038/339061a0

Type

Journal article

Journal

Nature

Publication Date

05/1989

Volume

339

Pages

61 - 64

Addresses

Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115.

Keywords

Cell Line, Edetic Acid, Membrane Glycoproteins, Cell Adhesion Molecules, Lymphocyte Function-Associated Antigen-1, DNA, RNA, Messenger, Antigens, Differentiation, Antigens, CD, Antibodies, Monoclonal, Antigens, Surface, Cloning, Molecular, Transfection, Nucleic Acid Hybridization, Cell Adhesion, Amino Acid Sequence, Base Sequence, Sequence Homology, Nucleic Acid, Genetic Vectors, Plasmids, Molecular Sequence Data