International Immunology Advance Access published online on March 28, 2006
International Immunology, doi:10.1093/intimm/dxl011
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1 Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia; Cooperative Research Centre for Vaccine Technology, Melbourne, Victoria 3050, Australia
* To whom correspondence should be addressed. CIRE/mDC-SIGN is a C-type lectin we originally identified as a molecule differentially expressed by mouse dendritic cell (DC) populations. Immunostaining with a CIRE/mDC-SIGN-specific mAb revealed that CIRE/mDC-SIGN is indeed on the surface of some CD4+, CD4-8- DCs and plasmacytoid pre-DCs, but not on CD8+ DCs. It has been proposed that CIRE/mDC-SIGN is the functional orthologue of human DC-SIGN (hDC-SIGN), a molecule that both enhances T cell responses and facilitates antigen uptake. We assessed if CIRE/mDC-SIGN and hDC-SIGN exhibit functional similarities. CIRE/mDC-SIGN is down-regulated upon activation, but unlike hDC-SIGN, incubation with IL-4 and IL-13 did not enhance CIRE/mDC-SIGN expression, indicating differences in gene regulation. Like hDC-SIGN, CIRE/mDC-SIGN bound mannosylated residues. However, we could detect no role for CIRE/mDC-SIGN in T cell-DC interactions and the protein did not bind to pathogens known to interact with hDC-SIGN, including Leishmania mexicana, cytomegalovirus, HIV and lentiviral particles bearing the Ebolavirus glycoprotein. The binding of CIRE/mDC-SIGN to hDC-SIGN ligands was not rescued when CIRE/mDC-SIGN was engineered to express the stalk region of hDC-SIGN. We conclude that there are significant differences in the fine specificity of the C-type lectin domains of hDC-SIGN and CIRE/mDC-SIGN and that these two molecules may not be functional orthologues.
Received June 5, 2005
Accepted February 16, 2006
Article
Functional comparison of mouse CIRE/mouse DC-SIGN and human DC-SIGN
Irina Caminschi 1,
Alexandra J. Corbett 2,
Corina Zahra 3,
Mireille Lahoud 3,
Karen M. Lucas 1,
Mariam Sofi 4,
David Vremec 3,
Thomas Gramberg 5,
Stefan Pöhlmann 5,
Joan Curtis 3,
Emanuela Handman 3,
Serani L. H. van Dommelen 6,
Peter Fleming 6,
Mariapia A. Degli-Esposti 6,
Ken Shortman 1,
and
Mark D. Wright 4 *
2 Centre for Experimental Immunology, Lions Eye Institute, Western Australia
3 Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria 3050, Australia
4 Mac Farlane Burnet Institute for Medical Research and Public Health, Kronheimer Building, A&RMC, Studley Road Heidelberg, Victoria 3084, Australia
5 Institute for Clinical and Molecular Virology and Nikolaus-Fiebiger Center, University of Erlangen-Nürnberg, 91054 Erlangen, Germany
6 Centre for Experimental Immunology, Lions Eye Institute, Western Australia; Immunology and Virology Program, Centre for Ophthalmology and Visual Science, University of Western Australia, Western Australia
Mark D. Wright, E-mail: caminschi{at}wehi.edu.au
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