The epithelial cellular adhesion molecule (Ep-CAM) is a ligand for the leukocyte-associated immunoglobulin-like receptor (LAIR).
Human leukocyte-associated immunoglobulin-like receptor (LAIR)-1 is expressed on many cells of the immune system and is predicted to mediate inhibitory functions based on the presence of immunoreceptor tyrosine-based inhibitory motifs (ITIMs) in its cytoplasmic domain. Although the role of LAIR-1 in the regulation of immune responses in vivo is unknown, LAIR-1 cross-linking by monoclonal antibody inhibits various immune cell functions in vitro. Here, we identify the colon carcinoma-associated epithelial cellular adhesion molecule (Ep-CAM) as a ligand for LAIR-1 and LAIR-2, a related soluble LAIR-1 family member. Ep-CAM interacts with the LAIR molecules through its first epidermal growth factor domain; Ep-CAM--specific antibodies can abrogate the binding. Intraepithelial T lymphocytes express LAIR-1 and thus may interact with Ep-CAM present on human intestinal epithelium. We propose that LAIR-1--Ep-CAM interaction may contribute to mucosal tolerance and that LAIR-2 possibly modulates this function.
Meyaard
L
L
Department of Immunology, University Medical Center, 3584 CX Utrecht, Netherlands. l.meyaard@lab.azu.nl
van der Vuurst de Vries
A R
AR
de Ruiter
T
T
Lanier
L L
LL
Phillips
J H
JH
Clevers
H
H
D000951:Antigens, Neoplasm / Q000378:metabolism*; D001665:Binding Sites; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D002478:Cells, Cultured; D000071858:Epithelial Cell Adhesion Molecule; D004847:Epithelial Cells / Q000502:physiology; D006801:Humans; D008024:Ligands; D008214:Lymphocytes / Q000502:physiology; D017434:Protein Structure, Tertiary; D011971:Receptors, Immunologic / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
D000951:Antigens, Neoplasm; D015815:Cell Adhesion Molecules; D000071858:Epithelial Cell Adhesion Molecule; C431503:LAIR-2 receptor; D008024:Ligands; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; C108073:leukocyte-associated immunoglobulin-like receptor 1