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 cruci al to the understanding of most immune reactions. Three human chemokines [I -309, thymus and activation-regulated chemokine (TARC) and macrophage infla mmatory protein-1 beta (MIP-1 beta)] have been reported to be ligands for C C-chemokine receptor 8 (CCR8). In this report, we present evidence that TAR C and MIP-1 beta, did not bind to or induce chemotaxis through CCR8 on a st able transfected cell line (1D-21) and did not bind to CCR8 on in vitro dif ferentiated human CD4(+) Th-2 cell cultures. Also, I-309-dependent calcium mobilization in 1D-21 cells and in Th, cells was desensitized by I-309 but not by MIP-1 beta or TARC. These results provide strong evidence that, at p hysiologically relevant concentrations, I-309 is the only known human ligan d for CCR8. These data also provide a framework for suggesting minimum requ irements for the assignment of chemokine receptor-ligand pairs.