The Journal of Experimental Medicine
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Published online 2 July 2001. doi:10.1084/jem.194.1.107
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© The Rockefeller University Press, 0022-1007/2001/7/107/ $5.00
The Journal of Experimental Medicine, Volume 194, Number 1, July 2, 2001 107-112

Brief Definitive Report

The Epithelial Cellular Adhesion Molecule (EP-Cam) Is a Ligand for the Leukocyte-Associated Immunoglobulin-like Receptor (Lair)

Linde Meyaarda, Anne-Renée van der Vuurst de Vriesa, Talitha de Ruitera, Lewis L. Lanierc, Joseph H. Phillipsb, and Hans Cleversa

a Department of Immunology, University Medical Center, 3584 CX Utrecht, Netherlands
b Department of Immunobiology, DNAX Research Institute, Palo Alto, CA 94304
c Department of Microbiology and Immunology and the Cancer Research Institute, University of California, San Francisco, CA 94304
Department of Immunology, University Medical Center, Heidelberglaan 100, Rm. F03.821, 3584 CX Utrecht, Netherlands.31-30-251710731-30-2507674

l.meyaard{at}lab.azu.nl

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 coloncarcinoma-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.

Key Words: ITIM • colon carcinoma • inhibitory receptor • intraepithelial lymphocytes • mucosal tolerance

© 2001 The Rockefeller University Press


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