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Mucosal Immunol. 2014 May;7(3):615-24. doi: 10.1038/mi.2013.80. Epub 2013 Oct 9.

Characterizing CEACAM5 interaction with CD8α and CD1d in intestinal homeostasis.

Author information

1
Immunology Institute, Mount Sinai School of Medicine, New York, New York, USA.
2
Goodman Cancer Center and Department of Biochemistry, McGill University, Montreal, Quebec, Canada.

Abstract

Normal intestinal epithelial cells (IECs) could act as non-professional antigen-presenting cells, selectively activating CD8(+)-suppressor T cells. An epithelial cell surface glycoprotein, gp180, recognized by monoclonal antibodies B9 and L12 was determined to be critical in this process. Purification and sequence analysis of mAb B9 reactive material revealed amino-acid sequence homology with CEACAM5. We demonstrate that CEACAM5 has properties attributed to gp180, such as CD8α binding and activation of CD8-associated Lck. CEACAM5 is the only CEACAM member interacting with CD1d through the B3 domain. Its N domain (recognized by B9) is required for CD8α binding. Removal of the N-domain glycosylated residues reduces B9 recognition, CD8α binding affinity, and activation of LcK. Therefore, conformational changes in CEACAM5 glycosylation site are critical for its interaction with CD8α. CEACAM5-activated CD8(+) T cells acquire the ability to suppress the proliferation of CD4(+) T cells in vitro in the presence of interleukin (IL)-15 or IL-7. We provide new insights into the role of CEACAM5 and define its specific immunoregulatory properties among the CEACAMs expressed on IECs. We suggest that unique set of interactions between CEACAM5, CD1d, and CD8 render CD1d more class I-like molecule, facilitating antigen presentation and activation of CD8(+)-suppressor regulatory T cells.

PMID:
24104458
PMCID:
PMC3981948
DOI:
10.1038/mi.2013.80
[Indexed for MEDLINE]
Free PMC Article
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