SECONDARY LYMPHOID-TISSUE CHEMOKINE IS A FUNCTIONAL LIGAND FOR THE CC-CHEMOKINE RECEPTOR CCR7

Secondary Lymphoid-tissue Chemokine (SLC) is a recently identified CC chemokine that is constitutively expressed in various lymphoid tissues and is a potent and specific chemoattractant for lymphocytes. The SLC gene and the gene encoding another lymphocyte-specific CC chemokine, EBI1-ligand chemokine (ELC), form a mini-cluster at human chromosome 9 p13. Here, we show that SLC is a high affinity functional ligand for c hemokine receptor 7 (CCR7) that is expressed on T and B lymphocytes an d a known receptor for ELC. SLC induced a vigorous calcium mobilizatio n in murine L1.2 cells stably expressing human CCR7. SLC tagged with t he secreted form of alkaline phosphatase (SLC-SEAP) showed specific bi nding to CCR7 that was fully competed by SLC with an IC50 of 0.5 nM. S LC also induced a vigorous chemotactic response in CCR7-expressing L1. 2 cells with a typical bell-shaped dose-response curve and a maximal m igration at 10 nM. When assessed using CCR7-transfected L1.2 cells, SL C and ELC were essentially equivalent in terms of cross desensitizatio n in calcium mobilization via CCR7, cross-competition in binding to CC R7, and induction of chemotaxis via CCR7. SLC and ELC were also shown to fully share receptors expressed on cultured normal T cells known to express CCR7. Notably, however, SLC was somehow less efficient in cro ss-desensitization against ELC in calcium mobilization and in cross-co mpetition with ELC for binding when assessed using cultured normal T c ells. Thus, SLC and ELC, even though sharing only 32% amino acid ident ity, constitute a genetically and functionally highly related subgroup of CC chemokines.