Characterization of CDw92 as a member of the choline transporter-like protein family regulated specifically on dendritic cells.
CDw92 is a 70-kDa surface protein broadly expressed on leukocytes and endothelial cells. In this manuscript, we present the molecular cloning of the CDw92 molecule by using a highly efficient retroviral expression cloning system. Sequence analysis of the CDw92 cDNA revealed a length of 2679 bp. The 1959-bp open reading frame encodes a protein of 652 amino acids. Computational analysis of the CDw92 protein sequence indicates 10 transmembrane domains, three potential N-linked glycosylation sites, and an amino acid stretch in the C-terminal region that is related to the immunoreceptor tyrosine-based inhibitory motif. Comparison of the sequence of the CDw92 clone presented in this study with various database entries show that it is a C-terminal variant of human choline transporter-like protein 1, a member of a recently identified family of multitransmembrane surface proteins. Furthermore, we found that CDw92 is stably expressed on monocytes, PBLs, and endothelial cells, as we did not yet find modulation of expression by various stimuli on these cells. In contrast to this factor-independent expression of CDw92, we detected a specific regulation of CDw92 on monocyte-derived dendritic cells (Mo-DCs). Maturation of Mo-DCs by ionomycin or calcium ionophore resulted in down-regulation of CDw92 and incubation of these cells with IL-10 in a specific re-expression. Moreover, targeting of CDw92 on LPS-treated Mo-DCs by CDw92 mAb VIM15b augmented the LPS-induced IL-10 production 2.8-fold. Together, these data suggest a crucial role of the CDw92 protein in the biology and regulation of the function of leukocytes in particular DCs.
Wille
S
S
Institute of Immunology, Vienna International Research Cooperation Center at Novartis Forschungsinstitut, Vienna, Austria.
Szekeres
A
A
Majdic
O
O
Prager
E
E
Staffler
G
G
Stöckl
J
J
Kunthalert
D
D
Prieschl
E E
EE
Baumruker
T
T
Burtscher
H
H
Zlabinger
G J
GJ
Knapp
W
W
Stockinger
H
H
D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001483:Base Sequence; D018801:CD2 Antigens / Q000235:genetics* / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D003001:Cloning, Molecular; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011233:Precipitin Tests; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D018801:CD2 Antigens; C440218:CDw92 antigen; D016207:Cytokines; D026901:Membrane Transport Proteins; C065637:choline transporter