Cutting edge: Identification of a novel chemokine receptor that binds dendritic cell- and T cell-active chemokines including ELC, SLC, and TECK

被引:161
作者
Gosling, J
Dairaghi, DJ
Wang, Y
Hanley, M
Talbot, D
Miao, ZH
Schall, TJ
机构
[1] ChemoCentryx, Div Discovery Biol, San Carlos, CA 94070 USA
[2] ChemoCentryx, Div Mol Pharmacol, San Carlos, CA 94070 USA
关键词
D O I
10.4049/jimmunol.164.6.2851
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
引用
收藏
页码:2851 / 2856
页数:6
相关论文
共 17 条
[1]   A new class of membrane-bound chemokine with a CX(3)C motif [J].
Bazan, JF ;
Bacon, KB ;
Hardiman, G ;
Wang, W ;
Soo, K ;
Rossi, D ;
Greaves, DR ;
Zlotnik, A ;
Schall, TJ .
NATURE, 1997, 385 (6617) :640-644
[2]   Cloning, expression, and chromosomal mapping of a novel human CC-chemokine receptor (CCR10) that displays high-affinity binding for MCP-1 and MCP-3 [J].
Bonini, JA ;
Martin, SK ;
Dralyuk, F ;
Roe, MW ;
Philipson, LH ;
Steiner, DF .
DNA AND CELL BIOLOGY, 1997, 16 (10) :1249-1256
[3]   HHV8-encoded vMIP-I selectively engages chemokine receptor CCR8 - Agonist and antagonist profiles of viral chemokines [J].
Dairaghi, DJ ;
Fan, PA ;
McMaster, BE ;
Hanley, RR ;
Schall, TJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (31) :21569-21574
[4]   CCR7 coordinates the primary immune response by establishing functional microenvironments in secondary lymphoid organs [J].
Förster, R ;
Schubel, A ;
Breitfeld, D ;
Kremmer, E ;
Renner-Müller, I ;
Wolf, E ;
Lipp, M .
CELL, 1999, 99 (01) :23-33
[5]   Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization [J].
Gunn, MD ;
Kyuwa, S ;
Tam, C ;
Kakiuchi, T ;
Matsuzawa, A ;
Williams, LT ;
Nakano, H .
JOURNAL OF EXPERIMENTAL MEDICINE, 1999, 189 (03) :451-460
[6]   A chemokine expressed in lymphoid high endothelial venules promotes the adhesion and chemotaxis of naive T lymphocytes [J].
Gunn, MD ;
Tangemann, K ;
Tam, C ;
Cyster, JG ;
Rosen, SD ;
Williams, LT .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (01) :258-263
[7]   Identification and molecular characterization of fractalkine receptor CX(3)CR1, which mediates both leukocyte migration and adhesion [J].
Imai, T ;
Hieshima, K ;
Haskell, C ;
Baba, M ;
Nagira, M ;
Nishimura, M ;
Kakizaki, M ;
Takagi, S ;
Nomiyama, H ;
Schall, TJ ;
Yoshie, O .
CELL, 1997, 91 (04) :521-530
[8]  
Jenh CH, 1999, J IMMUNOL, V162, P3765
[9]   Cloning and characterization of a novel promiscuous human β-chemokine receptor D6 [J].
Nibbs, RJB ;
Wylie, SM ;
Yang, JY ;
Landau, NR ;
Graham, GJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1997, 272 (51) :32078-32083
[10]   Two subsets of memory T lymphocytes with distinct homing potentials and effector functions [J].
Sallusto, F ;
Lenig, D ;
Förster, R ;
Lipp, M ;
Lanzavecchia, A .
NATURE, 1999, 401 (6754) :708-712