Novel lymphocyte-specific CC chemokines and their receptors.

By using a cloning method termed the signal sequence trap as well as by searching for chemokine homologous sequences in the database of expressed sequence tags, cDNA fragments potentially encoding novel CC chemokines were initially identified. Using these sequences, we have cloned five novel human CC chemokines termed TARC, LARC, ELC, SLC, and PARC. These chemokines are constitutively expressed especially in some lymphoid tissues with individually unique expression patterns. The recombinant proteins are all found to be selectively chemotactic for lymphocytes 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 at chromosome 17q11.2, whereas those for TARC, LARC, ELC, and SLC are localized at different loci. Collectively, these five CC chemokines may constitute a new category of CC chemokines that are involved in trafficking and homing of particular subsets of lymphocytes in particular lymphoid tissue microenvironments.