C chemokine (IPR008105)
Short name: Chemokine_XCL1/XCL2
Overlapping homologous superfamilies
- Chemokine interleukin-8-like superfamily (IPR036048)
- Chemokine beta/gamma/delta (IPR039809)
- C chemokine (IPR008105)
Chemokines (chemotactic cytokines) are a family of chemoattractant molecules. They attract leukocytes to areas of inflammation and lesions, and play a key role in leukocyte activation. Originally defined as host defense proteins, chemokines are now known to play a much broader biological role [PMID: 11544102]. They have a wide range of effects in many different cell types beyond the immune system, including, for example, various cells of the central nervous system [PMID: 9689100], and endothelial cells, where they may act as either angiogenic or angiostatic factors [PMID: 7592998].
The chemokine family is divided into four classes based on the number and spacing of their conserved cysteines: 2 Cys residues may be adjacent (the CC family); separated by an intervening residue (the CXC family); have only one of the first two Cys residues (C chemokines); or contain both cysteines, separated by three intervening residues (CX3C chemokines).
Chemokines exert their effects by binding to rhodopsin-like G protein-coupled receptors on the surface of cells. Following interaction with their specific chemokine ligands, chemokine receptors trigger a flux in intracellular calcium ions, which cause a cellular response, including the onset of chemotaxis. There are over fifty distinct chemokines and least 18 human chemokine receptors [PMID: 10714678]. Although the receptors bind only a single class of chemokines, they often bind several members of the same class with high affinity. Chemokine receptors are preferentially expressed on important functional subsets of dendritic cells, monocytes and lymphocytes, including Langerhans cells and T helper cells [PMID: 10601351, PMID: 9500790]. Chemokines and their receptors can also be subclassified into homeostatic leukocyte homing molecules (CXCR4, CXCR5, CCR7, CCR9) versus inflammatory/inducible molecules (CXCR1, CXCR2, CXCR3, CCR1-6, CX3CR1).
The C chemokine subfamily is composed of two members, XC chemokine ligand 1 (XCL1), also known as lymphotactin or SCM-1 alpha, and XC chemokine ligand 2 (XCL2), also known as SCM-1 beta [PMID: 10714678]. The cognate receptor for these chemokines is XCR1 [PMID: 9632725].
XCL1 is an inflammatory chemokine that produced by activated CD8+ T cells and natural killer cells. It is involved in the mediation of interactions between antigen-presenting dendritic cells and T-cells, and induction of CD8+ effector T-cell responses [PMID: 19913446, PMID: 22100876]. It is also involved in the formation of self-tolerance mechanisms through the development of T regulatory cells within the thymus [PMID: 21300913]. Less is known about its closely related paralogue XCL2, although the in vitro functional profiles are virtually identical [PMID: 25497737]. Human XCL2 and XCL1 amino acid sequences differ at only two positions near the N terminus [PMID: 8849694].
Viral XCL1 (vXCL1) exclusively binds to CD4(-) rat dendritic cells (DC), a subset of DC that express the corresponding chemokine receptor XCR1, a strategy to subvert cytotoxic immune responses [PMID: 24155383].