Secondary Lymphoid-tissue Chemokine Is a Functional Ligand for the CC Chemokine Receptor CCR7

• Published in: The Journal of biological chemistry Vol. 273; no. 12; pp. 7118 - 7122
• Main Authors: Yoshida, Ryu, Nagira, Morio, Kitaura, Motoji, Imagawa, Noriko, Imai, Toshio, Yoshie, Osamu
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 20.03.1998
• Subjects: Amino Acid Sequence; Calcium - metabolism; Cells, Cultured; Chemokine CCL19; Chemokine CCL21; Chemokines, CC - metabolism; Chemotaxis, Leukocyte; Humans; Ligands; Lymphoid Tissue - metabolism; Molecular Sequence Data; Receptors, CCR7; Receptors, Chemokine - chemistry; Receptors, Chemokine - genetics; Receptors, Chemokine - metabolism; Sequence Alignment; T-Lymphocytes - metabolism; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.12.7118

S econdary L ymphoid-tissue C hemokine (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 9p13. Here, we show that SLC is a high affinity functional ligand for chemokine receptor 7 (CCR7) that is expressed on T and B lymphocytes and a known receptor for ELC. SLC induced a vigorous calcium mobilization in murine L1.2 cells stably expressing human CCR7. SLC tagged with the secreted form of alkaline phosphatase (SLC-SEAP) showed specific binding to CCR7 that was fully competed by SLC with an IC 50 of 0.5 n m . SLC also induced a vigorous chemotactic response in CCR7-expressing L1.2 cells with a typical bell-shaped dose-response curve and a maximal migration at 10 n m . When assessed using CCR7-transfected L1.2 cells, SLC and ELC were essentially equivalent in terms of cross desensitization in calcium mobilization via CCR7, cross-competition in binding to CCR7, 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 cross-desensitization against ELC in calcium mobilization and in cross-competition with ELC for binding when assessed using cultured normal T cells. Thus, SLC and ELC, even though sharing only 32% amino acid identity, constitute a genetically and functionally highly related subgroup of CC chemokines.