Functional cloning of ICAM-2, a cell adhesion ligand for LFA-1 homologous to ICAM-1.
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.
Staunton
D E
DE
Department of Pathology, Harvard Medical School, Boston, Massachusetts 02115.
Dustin
M L
ML
Springer
T A
TA
D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000378:metabolism*; D000954:Antigens, Surface / Q000235:genetics* / Q000276:immunology; D001483:Base Sequence; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D004492:Edetic Acid; D005822:Genetic Vectors; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D008969:Molecular Sequence Data; D009693:Nucleic Acid Hybridization; D010957:Plasmids; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012689:Sequence Homology, Nucleic Acid; D014162:Transfection
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D015815:Cell Adhesion Molecules; C065289:ICAM2 protein, human; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D004247:DNA; D004492:Edetic Acid