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 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 IC50 of 0.5 nM. 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 nM. 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.
Yoshida
R
R
Shionogi Institute for Medical Science, 2-5-1 Mishima, Settsu-shi, Osaka 566, Japan.
Nagira
M
M
Kitaura
M
M
Imagawa
N
N
Imai
T
T
Yoshie
O
O
D000595:Amino Acid Sequence; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC / Q000378:metabolism*; D002634:Chemotaxis, Leukocyte; D006801:Humans; D008024:Ligands; D008221:Lymphoid Tissue / Q000378:metabolism*; D008969:Molecular Sequence Data; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D013601:T-Lymphocytes / Q000378:metabolism; D014162:Transfection
C515460:CCL19 protein, human; C515478:CCL21 protein, human; C515370:CCR7 protein, human; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D019742:Chemokines, CC; D008024:Ligands; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D002118:Calcium