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 endot helial cells. In this manuscript, we present the molecular cloning of the C Dw92 molecule by using a highly efficient retroviral expression cloning sys tem. 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. Computatio nal analysis of the CDw92 protein sequence indicates 10 transmembrane domai ns, three potential N-linked glycosylation sites, and an amino acid stretch in the C-terminal region that is related to the immunoreceptor tyrosine-ba sed inhibitory motif. Comparison of the sequence of the CDw92 clone present ed 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 recentl y identified family of multitransmembrane surface proteins. Furthermore, we found that CDw92 is stably expressed on monocytes, PBLs, and endothelial c ells, as we did not yet find modulation of expression by various stimuli on these cells. In contrast to this factor-independent expression of CDw92, w e detected a specific regulation of CDw92 on monocyte-derived dendritic cel ls (Mo-DCs). Maturation of Mo-DCs by ionomycin or calcium ionophore resulte d 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. T ogether, these data suggest a crucial role of the CDw92 protein in the biol ogy and regulation of the function of leukocytes in particular DCs.