NOVEL LYMPHOCYTE-SPECIFIC CC CHEMOKINES AND THEIR RECEPTORS

By using a cloning method termed the signal sequence trap as well as b y searching for chemokine homologous sequences in the database of exb pressed sequence tags, cDNA fragments potentially encoding novel CC ch emokines were initially identified, Using these sequences, we have clo ned five novel human CC chemokines termed TARC, LARC, ELC, SLC, and PA RC. These chemokines are constitutively expressed especially in some l ymphoid tissues with individually unique expression patterns, The reco mbinant proteins are all found to be selectively chemotactic for lymph ocytes but not for monocytes or neutrophils, Each chemokine appears to interact with a class of receptors on lymphocytes that is not shared by any other chemokines so far tested, Furthermore, we have identified CCR4 as the specific receptor for TARC, GPR-CY4/DRY6/CKR-L3/STRL22 as that for LARC (CCR6), and EBI1/BLR2 as that for ELC (CCR7), Only the gene for PARC is mapped to the traditional CC chemokine gene cluster a t chromosome 17q11.2, whereas those for TARC, LARC, ELC, and SLC are l ocalized at different loci, Collectively, these five CC chemokines may constitute a new category of CC chemokines that are involved in traff icking and homing of particular subsets of lymphocytes in particular l ymphoid tissue microenvironments.