摘要 |
CDw92 is a cell surface protein with a size of 70 kDa which is expressed on numerous leukocytes and endothelial cells. The invention relates to a method for the molecular cloning of the CDw92 molecule using a highly efficient retroviral expression cloning system. Sequence analysis of the CDw92 cDNA established a length of 2679 base pairs. The open reading frame (ORF) having a size of 1959 bp contains the code for a protein with 652 AA. A computer-assisted analysis of the protein sequence of CDw92 established 10 transmembrane domains, three potential N glycosylation sites and one section in the C-terminal domain that is related to ITM (immunoreceptor tyrosine-based inhibitory motif). A comparison of the sequence of the CDw92 clone hereby found with various data base entries had the result that it is a C-terminal variant of the human choline transporter-like protein 1 that belongs to a family of surface proteins with several transmembrane domains recently identified. It was furthermore found that CDw92 is stably expressed on the surface of monocytes, PBLs and endothelial cells since so far no modulation of expression could be established for these cells using various stimulating substances. Contrary to this factor-independent expression of CDw92, a specific regulation of CDw92 was detected on the surface of monocyte-derived dendritic cells (Mo-DCs). During maturation of the Mo-DCs under the influence of ionomycine or calcium ionophore a down-regulation of CDw92 was observed and a specific new expression took place when these cells were incubated with IL-10. The addition of CDw92-mAks VIM15b to LPS-treated Mo-DCs led to an increase in LPS-induced IL-10 production by 2.8. In summary, these data furnish evidence for the critical role of the CDw92 protein for the field of biology and the regulation of the function of leukocytes, especially of dendritic cells. |
申请人 |
BMT MEDIZINISCHE FORSCHUNG UND ENTWICKLUNG GMBH;STOCKINGER, HANNES;WILLE, STEFAN;SZEKERES, ANDREAS;MAJDIC, OTTO;PRAGER, ELISABETH;STAFFLER, GUENTHER;STOECKL, JOHANNES;KUNTHALERT, DUANGKAMOL;PRIESCHL, EVA, E.;BAUMRUKER, THOMAS;BURTSCHER, HELMUT;ZLABINGER, GERHARD, J.;KNAPP, WALTER |
发明人 |
STOCKINGER, HANNES;WILLE, STEFAN;SZEKERES, ANDREAS;MAJDIC, OTTO;PRAGER, ELISABETH;STAFFLER, GUENTHER;STOECKL, JOHANNES;KUNTHALERT, DUANGKAMOL;PRIESCHL, EVA, E.;BAUMRUKER, THOMAS;BURTSCHER, HELMUT;ZLABINGER, GERHARD, J.;KNAPP, WALTER |