Functional Cloning of ICAM-2, a Cell Adhesion Ligand for LFA-1 Homologous to ICAM-1

Nature. 1989 May 4;339(6219):61-4. doi: 10.1038/339061a0.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Antibodies, Monoclonal
  • Antigens, CD
  • Antigens, Differentiation
  • Antigens, Surface
  • Cell Adhesion Molecules
  • ICAM2 protein, human
  • Lymphocyte Function-Associated Antigen-1
  • Membrane Glycoproteins
  • RNA, Messenger
  • DNA
  • Edetic Acid

Associated data

  • GENBANK/X15606