Functional comparison of mouse CIRE/mouse DC-SIGN and human DC-SIGN.
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.
Walter and Eliza Hall Institute of Medical Research Melbourne, Victoria 3050, Australia. caminschi@wehi.edu.au
Irina
I
Caminschi
Alexandra J
AJ
Corbett
Corina
C
Zahra
Mireille
M
Lahoud
Karen M
KM
Lucas
Mariam
M
Sofi
David
D
Vremec
Thomas
T
Gramberg
Stefan
S
Pöhlmann
Joan
J
Curtis
Emanuela
E
Handman
Serani L H
SL
van Dommelen
Peter
P
Fleming
Mariapia A
MA
Degli-Esposti
Ken
K
Shortman
Mark D
MD
Wright
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D016466:CHO Cells; D015815:Cell Adhesion Molecules / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D006224:Cricetinae; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D037181:Lectins, C-Type / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D008024:Ligands; D008358:Mannose / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin
D000911:Antibodies, Monoclonal; D015815:Cell Adhesion Molecules; D037181:Lectins, C-Type; D008024:Ligands; D008358:Mannose; D011956:Receptors, Cell Surface; D000099215:DC-Specific ICAM-3 Grabbing Nonintegrin