XCL2

XCL2 (also knowns as SCM1-β and SCYC-2) is a member of C chemokine sub-family that is highly related to XCL1. XCL2 binds and activates the G protein-coupled receptor, XCR1. XCL2 is constitutively expressed by unstimulated natural killer (NK) cells and to a lesser extent by inactive CD8⁺ T cells^[1].
Structurally, XCL1 and XCL2 are very similar, exchanging between the monomeric chemokine fold and an unrelated dimeric state under physiological NaCl and temperature conditions. XCL1 and XCL2 mapped to chromosome 1, and RT-PCR analysis revealed XCL1 and XCL2 transcripts in both mitogen stimulated and non-stimulated cells. Ca²⁺ flux, chemotaxis, and heparin binding assays showed that the monomer form of XCL2 is responsible for G protein-coupled receptor activation while the dimeric form is important for GAG binding. Furthermore, XCL2 displays a slightly higher affinity for heparin than XCL1. Activation of T cells resulted in a dramatic increase in XCL1 and XCL2 expression in CD8⁺ T cells. Activated CD4⁺ T cells demonstrated increased amounts of XCL2, but not XCL1^[1].
Binding of XCL2 to XCR1 initiates chemotaxic cell migration in dendritic cells as well as in T and B lymphocytes. XCL2 is also induced by cancer and bacterial pathogens. In cancers such as epithelial ovarian and hepatocellular carcinoma, increased XCL2 expression correlates with cancer progression. In a separate study, addition of a tuberculosis antigen, Wag31 induced the expression of XCL2 but not XCL1 in macrophages^[1].

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