Chemokine receptors interactions with

M.J. Smit, H. Timmerman, D. VerzijI, R. Leurs Chemokine receptors interaction with FIIV-1 and viral-encoded chemokines... 

Chemokine receptors interaction with HIV-1 and viral-encoded... 

The organization of chemokine families based on the cysteine sequence has functional significance. Some human chemokines can compete for binding and activation of receptors with other intrafamily chemokines. This raised the possibility that significant structural differences in chemokine-receptor interactions... 

Wu L, LaRosa G, Kassam N, et al. Interaction of chemokine receptor CCR5 with its ligands multiple domains for HIV-1 gpl20 binding and a single domain for chemokine binding. J Exp Med 1997 186(8) 1373—1381. 

Regrettably, the receptor classification system is much more complex than this. For example, the chemokine class of cytokine receptors is further subdivided into at least 16-20 different receptor subtypes, including CCRl, CCR2. .. CCRll, CXCRl, CXCR2. .. CXCR5. These receptors interact with more than 25-30 different types of chemokines. 

MCCH can utilize a variety of CC and CXC chemokine receptors. Interaction has been specifically demonstrated with CCR1 and/or CCR5, CCR2, CCR8, CXCR1, and/or CXCR2 and CXCR4 (Damon et al., 1998). 

Blaszczyk,J., Goillie, E. V., Proost, P., Damme.J. V., Opdenakker, G., Bujacz, G. D., Wang, J. M., andji, X. (2000). Gomplete crystal structure of monocyte chemotactic protein-2, a GG chemokine that interacts with multiple receptors. Biochem. 39, 14075—14081. 

Interestingly, there is a certain degree of promiscuity in the chemokine superfamily with many ligands binding different receptors or vice versa. So-called cluster chemokines representing chemotactic proteins which share a distinct chromosomal location are likely to bind the same receptors. However, noncluster or microcluster chemokines are ligands which demonstrate a unique chromosomal location and tend to present a restricted or even specific chemokine receptor interaction [23]. 

Strong, A. E., Thierry, A. C., Cousin, P., Moulon, C., Demotz, S. (2006). Synthetic chemokines direcdy labeled with a fluorescent dye as tools for studying chemokine and chemokine receptor interactions. European Cytokine Network, 17, 49-59. 

In addition, the injected chemokine may interact with and activate resident cells, such as macrophages, leading to the generation of intermediate chemoattractant molecules that will themselves activate their receptor on the surface of leukocytes (Sokol Luster, 2015). 

Figure 1 Schematic representation of DC traffic from the periphery to the draining LN (DLN) and the potential mechanisms for HS in this process. Immature DCs (imDC) pick up antigen in the periphery, undergo maturation to become mature DCs (maDC), and are associated with the upregulation of certain chemokine receptors, such as CCR7. Following HS-mediated chemokine gradients, lymphatic flow, and adhesion events that may also be mediated by lymphatic endothelial HS, antigen-loaded DCs travel from the periphery to the DLN, where they present antigen to T cells and modulate the balance between immune activation and immune tolerance. Importantly, HS on soluble proteoglycans may also mediate chemokine—receptor interactions in trans.

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