C-C Motif Chemokine 21a (CCL21a) is a small secreted cytokine that belongs to the intercrine beta (CC chemokine) family. Mouse CCL21 cDNA encodes a 133 amino acid residue protein with a 23 residue signal peptide that is cleaved to generate the 110 residue mature protein. Mouse CCL21 has three forms while CCL21a has Ser-65. CCL21 elicits its effects by binding to a cell surface chemokine receptor known as CCR7 and CXCR3. Mouse CCL21 inhibits hemopoiesis and stimulates chemotaxis. It has chemotactic function in vitro for thymocytes and activated T-cells, but not for B-cells, macrophages, or neutrophils. Mouse CCL21 shows preferential activity towards naive T-cells and may play a role in mediating homing of lymphocytes to secondary lymphoid organs.
CCL22, also named stimulated T cell chemotactic protein (STCP-1) and MDC, is a CC chemokine initially isolated from clones of monocyte-derived macrophages. Human CCL22 cDNA encodes a precursor protein of 93 amino acid residues with an a 24 amino acid residue predicted signal peptide that is cleaved to yield a 69 amino acid residue mature 8 kDa protein. At the amino acid sequence level, CCL22 shows less than 35% identity to other CC chemokine family members. Human CCL22 is expressed in dendritic cells, macrophages and activated monocytes. In addition, CCL22 expression is also detected in the tissues of thymus, lymph node and appendix. The gene for human CCL22 has been mapped to chromosome 16 rather than chromosome 17 where the genes for many human CC chemokines are clustered. Recombinant or chemically synthesized mature CCL22 has been shown to induce chemotaxis or Ca2+ mobilization in dendritic cells, IL-2 activated NK cells, and activated T lymphocytes. A CD8+ T lymphocyte-derived secreted soluble activity that suppresses infection by primary non-syncytium-inducing and syncytium-inducing HIV-1 isolates and the T cell line-adapted isolate HIV-1IIIB, has been identified as CCL22. Based on amino-terminal sequence analysis, the major CD8+ T lymphocyte-derived CCL22 protein yielded an amino-terminal sequence of YGANM, which is two amino acid residues shorter than the predicted mature CCL22. The difference in potency between the two mature CCL22 isoforms has not been determined.
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