IDENTIFICATION OF CCR8 - A HUMAN MONOCYTE AND THYMUS RECEPTOR FOR THECC CHEMOKINE I-309

The human CC chemokine 1-309 is a potent monocyte chemoattractant and inhibits apoptosis in thymic cell lines. Here, we identify a specific human 1-309 receptor, and name it CCR8 according to an accepted nomenc lature system. The receptor has seven predicted transmembrane domains, is expressed constitutively in monocytes and thymus, and is encoded b y a previously reported gene of previously unknown function named, alt ernatively, CY6, TER1, and CKR-L1. After transfection with the CY6 ope n reading frame, a mouse pre-B cell line exhibited calcium flux and ch emotaxis in response to 1-309 (EC50 = 2 nM for each), whereas 20 other chemokines were inactive. Signaling was sensitive to pertussis toxin, suggesting coupling to a Gi-type G protein. These properties parallel those of endogenous 1-309 receptors expressed in an HL-60 clone 15 ce ll line model. The apparent monogamous relationship between I-309 and CCR8 is unusual among known CC chemokines and known CC chemokine recep tors. CCR8 may regulate monocyte chemotaxis and thymic cell line apopt osis.