Molecular cloning of ICAM-3, a third ligand for LFA-1, constitutively expressed on resting leukocytes.
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 types. Leukocyte function-associated antigen 1 (LFA-1) is expressed on the surface of all white blood cells and is a receptor for intercellular adhesion molecules (ICAM) 1 and 2 (ref. 3) which are members of the immunoglobulin superfamily. 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 lymphocytes and cytotoxic T cells and their targets. In addition, both ICAMs are expressed at low levels on resting vascular endothelium; ICAM-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.
Fawcett
J
J
ICRF Laboratories, University of Oxford, UK.
Holness
C L
CL
Needham
L A
LA
Turley
H
H
Gatter
K C
KC
Mason
D Y
DY
Simmons
D L
DL
D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation; D001402:B-Lymphocytes; D001483:Base Sequence; D015815:Cell Adhesion Molecules / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004730:Endothelium, Vascular / Q000502:physiology; D005091:Exons; D015723:Gene Library; D006801:Humans; D007074:Immunoglobulin G / Q000235:genetics; D007962:Leukocytes / Q000502:physiology*; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1 / Q000302:isolation & purification / Q000378:metabolism*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000302:isolation & purification / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014162:Transfection; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D000943:Antigens, Differentiation; D015815:Cell Adhesion Molecules; C483616:ICAM3 protein, human; D007074:Immunoglobulin G; D008024:Ligands; D016169:Lymphocyte Function-Associated Antigen-1; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins