6Ckine is a novel CC chemokine discovered independently by three groups from the EST database. 6Ckine, also named SLC (Secondary Lymphoid-tissue Chemokine), CCL21, and Exodus-2, shows 21-33% identity to other CC chemokines. 6Ckine contains the four conserved cysteines characteristic of beta chemokines plus two additional cysteines in its unusually long carboxyl-terminal domain. Human 6Ckine cDNA encodes a 134 amino acid (aa) residue, highly basic, precursor protein with a 23 aa residue signal peptide that is cleaved to form the predicted 111 aa residue mature protein. Mouse 6Ckine cDNA encodes a 133 aa residue protein with a 23 residue signal peptide that is cleaved to generate the 110 residue mature protein. Human and mouse 6Ckine are highly conserved, exhibiting 86% aa sequence identity. 6Ckine is constitutively expressed at high levels in lymphoid tissues such as lymph nodes, spleen, and appendix. In mouse, high levels of 6Ckine mRNA are also detected in the lung. The gene for human 6Ckine has been localized at human chromosome 9p13 rather than chromosome 17 where the genes of many human CC chemokines are clustered. The 6Ckine gene location is within a region of about 100 kb from the gene for MIP-3 beta /ELC, another novel CC chemokine.
Unlike most CC chemokines, 6Ckine is not chemotactic for monocytes. Recombinant mouse 6Ckine is chemotactic in vitro for thymocytes and activated T cells. Recombinant human 6Ckine has been shown to be chemotactic for some human T cell lines, resting PBL, and cultured T cells expanded with PHA and IL-2. 6Ckine has also been reported to inhibit hemopoietic progenitor colony formation in a dose-dependent manner. 6Ckine acts via a class of as yet unidentified CC receptors on both T cells and B cells that are not shared by any other CC chemokines so far tested.
