Cutting edge: identification of a novel chemokine receptor that binds dendritic cell- and T cell-active chemokines including ELC, SLC, and TECK.
Searching for new receptors of dendritic cell- and T cell-active chemokines, we used a combination of techniques to interrogate orphan chemokine receptors. We report here on human CCX CKR, previously represented only by noncontiguous expressed sequence tags homologous to bovine PPR1, a putative gustatory receptor. We employed a two-tiered process of ligand assignment, where immobilized chemokines constructed on stalks (stalkokines) were used as bait for adhesion of cells expressing CCX CKR. These cells adhered to stalkokines representing ELC, a chemokine previously thought to bind only CCR7. Adhesion was abolished in the presence of soluble ELC, SLC (CCR7 ligands), and TECK (a CCR9 ligand). Complete ligand profiles were further determined by radiolabeled ligand binding and competition with >80 chemokines. ELC, SLC, and TECK comprised high affinity ligands (IC50 <15 nM); lower affinity ligands include BLC and vMIP-II (IC50 <150 nM). With its high affinity for CC chemokines and homology to CC receptors, we provisionally designate this new receptor CCR10.
Gosling
J
J
Divisions of Discovery Biology and Molecular Pharmacology, ChemoCentryx, San Carlos, CA 94070, USA.
Dairaghi
D J
DJ
Wang
Y
Y
Hanley
M
M
Talbot
D
D
Miao
Z
Z
Schall
T J
TJ
D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D002448:Cell Adhesion / Q000235:genetics / Q000276:immunology; D002460:Cell Line; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000378:metabolism*; D003001:Cloning, Molecular; D003713:Dendritic Cells / Q000378:metabolism*; D006801:Humans; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D011485:Protein Binding; D012333:RNA, Messenger / Q000096:biosynthesis; D011869:Radioligand Assay; D054447:Receptors, CCR10; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification* / Q000378:metabolism*; D013601:T-Lymphocytes / Q000378:metabolism*; D014162:Transfection
C515460:CCL19 protein, human; C515478:CCL21 protein, human; C108074:CCL25 protein, human; C515706:CCR10 protein, human; C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; C491541:Ccl25 protein, mouse; C515707:Ccr10 protein, mouse; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC; D012333:RNA, Messenger; D054447:Receptors, CCR10; D019707:Receptors, Chemokine