The assignment of chemokine-chemokine receptor pairs: TARC and MIP-1 beta are not ligands for human CC-chemokine receptor 8.
Identification of chemokine receptors and their associated ligands is crucial to the understanding of most immune reactions. Three human chemokines [I-309, thymus and activation-regulated chemokine (TARC) and macrophage inflammatory protein-1beta (MIP-1beta)] have been reported to be ligands for CC-chemokine receptor 8 (CCR8). In this report, we present evidence that TARC and MIP-1beta did not bind to or induce chemotaxis through CCR8 on a stable transfected cell line (1D-21) and did not bind to CCR8 on in vitro differentiated human CD4(+) Th(2) cell cultures. Also, I-309-dependent calcium mobilization in 1D-21 cells and in Th(2) cells was desensitized by I-309 but not by MIP-1beta or TARC. These results provide strong evidence that, at physiologically relevant concentrations, I-309 is the only known human ligand for CCR8. These data also provide a framework for suggesting minimum requirements for the assignment of chemokine receptor-ligand pairs.
Garlisi
C G
CG
Allergy and Immunology, Schering-Plough Research Institute, Kenilworth 07033-0539, USA. charles.garlisi@spcorp.com
Xiao
H
H
Tian
F
F
Hedrick
J A
JA
Billah
M M
MM
Egan
R W
RW
Umland
S P
SP
D015704:CD4 Antigens / Q000096:biosynthesis / Q000235:genetics; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D054414:Chemokine CCL17; D054407:Chemokine CCL4; D019742:Chemokines, CC / Q000276:immunology / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte / Q000276:immunology; D004247:DNA / Q000235:genetics; D006801:Humans; D008024:Ligands; D019402:Macrophage Inflammatory Proteins / Q000276:immunology / Q000378:metabolism*; D054401:Receptors, CCR8; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014162:Transfection
C106230:CCL17 protein, human; C103330:CCR8 protein, human; D015704:CD4 Antigens; D054414:Chemokine CCL17; D054407:Chemokine CCL4; D019742:Chemokines, CC; D008024:Ligands; D019402:Macrophage Inflammatory Proteins; D054401:Receptors, CCR8; D019707:Receptors, Chemokine; D004247:DNA; D002118:Calcium