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. 2001 Jul 2;194(1):107-12.
doi: 10.1084/jem.194.1.107.

The epithelial cellular adhesion molecule (Ep-CAM) is a ligand for the leukocyte-associated immunoglobulin-like receptor (LAIR)

L Meyaard  1 , A R van der Vuurst de Vries, T de Ruiter, L L Lanier, J H Phillips, H Clevers
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The epithelial cellular adhesion molecule (Ep-CAM) is a ligand for the leukocyte-associated immunoglobulin-like receptor (LAIR)

L Meyaard et al. J Exp Med. .

Retraction in

  • Retraction.
    Meyaard L, van der Vuurst de Vries AR, de Ruiter T, Lanier LL, Phillips JH, Clevers H. Meyaard L, et al. J Exp Med. 2003 Oct 6;198(7):1129. doi: 10.1084/jem.200309031941107cor. Epub 2003 Sep 29. J Exp Med. 2003. PMID: 14517276 Free PMC article. No abstract available.

Abstract

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.

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Figures

Figure 1
Figure 1
LAIR-1L is identical to Ep-CAM. (A) LAIR-1-hIg binding to the colon carcinoma cell line HT29, demonstrating the presence of a putative LAIR-1L. (B) LAIR-1-hIg binding to 293T cells transfected with the LAIR-1L cDNA obtained by expression cloning from an HT29 cDNA library. (C) Ep-CAM expression on HT29 cells and (D) Ep-CAM expression on 293T cells transfected with the LAIR-1L cDNA clone. Filled histograms represent staining with LAIR-1-hIg (A and B) or FITC-conjugated anti–Ep-CAM mAb UBS54 (C and D). Open histogram represents staining with isotype control Abs (A and C) or staining of 293T cells transfected with an irrelevant cDNA (B and D).
Figure 2
Figure 2
Anti–Ep-CAM Abs inhibit binding of LAIR-1-hIg. HT29 cells were stained with LAIR-1-hIg or control hIg after prior incubation for 20 min at RT with 1 μg control (filled histogram) or anti–Ep-CAM 323/A3 F(ab′)2 fragments (open histogram). Dashed histogram represents staining with anti–Ep-CAM and control human IgG1.
Figure 4
Figure 4
LAIR binds to the first EGF domain of Ep-CAM. (A) Myc-tagged deletion constructs of human Ep-CAM (LK57-LK63) and wild-type human Ep-CAM (LK17) were transfected into 293T cells and binding of LAIR-1-hIg and LAIR-2-hIg was assessed by flow cytometry. Results are indicated with ++ for strong binding and − for absence of binding. The domains of Ep-CAM are indicated with boxes . Amino acids (aa) are indicated with numbers, starting from the first methionine. Leader, leader peptide (aa 1–22); EGF-1, EGF-like domain 1 (aa 27–59); EGF-2, EGF-like domain 2 (aa 66–135); TM, transmembrane region (aa 267–288); myc, myc tag. (B) Representative histograms of LAIR-1-hIg binding to 293T cells transfected with the constructs indicated. Cells were stained with LAIR-1-hIg (filled histograms) or control hIg (open histograms). The middle panel represents the binding to cells transfected with constructs LK57 through LK62. Similar results were obtained with LAIR-2-hIg (data not shown).
Figure 3
Figure 3
Both LAIR-1 and LAIR-2 bind Ep-CAM. LAIR-1-hIg (open histograms) and LAIR-2-hIg (dashed histograms) binding to the colon carcinoma cell line HT29 (A) and to 293T cells transfected with Ep-CAM cDNA (B). Filled histograms represent staining with control human IgG1.
Figure 5
Figure 5
LAIR-1 is expressed on human intestinal intraepithelial lymphocytes. (A) IELs isolated from colon stained with anti-CD3 and gated on CD3-positive cells. Filled histogram represents staining with anti–LAIR-1 mAb and open histogram with isotype control mAb. (B–E) Sections from human ileum were stained with anti–LAIR-1 mAb (red), anti-Ep-CAM mAb (green), and DAPI (blue), and analyzed on a fluorescence microscope. C and E are higher magnifications of the areas indicated in B and D, respectively. Intraepithelial lymphocytes are indicated with white arrows.
Figure 5
Figure 5
LAIR-1 is expressed on human intestinal intraepithelial lymphocytes. (A) IELs isolated from colon stained with anti-CD3 and gated on CD3-positive cells. Filled histogram represents staining with anti–LAIR-1 mAb and open histogram with isotype control mAb. (B–E) Sections from human ileum were stained with anti–LAIR-1 mAb (red), anti-Ep-CAM mAb (green), and DAPI (blue), and analyzed on a fluorescence microscope. C and E are higher magnifications of the areas indicated in B and D, respectively. Intraepithelial lymphocytes are indicated with white arrows.
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References

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