C-x-C and C-C chemokines mediate their effects on leukocytes by binding to high affinity G-protein coupled receptors which contain seven transmembrane domains which span the cell membrane.
Cloned chemokine receptors show three types of binding.
Promiscuous chemokine receptors such as the erythroid chemokine receptor (ECKR, the Duffy A blood group antigen) binds many C-x-C and C-C chemokines.
Specific chemokine receptors bind only one chemokine ligand, examples are the IL-8 receptor A (IL-8 RA) and the MCP-1 receptor CCR2.
Shared chemokine receptors expressed in transfected cells bind more than one chemokine with high affinity, the best characterised examples are the IL-8 receptor B (IL-8 RB) which binds many of the identified C-X-C chemokines and CCR1 which binds and induces Ca2+ flux in response to 10-100nM concentrations of MIP-1a and RANTES.
An important goal of current research is to identify which chemokine receptors effect the responses of leukocytes to chemokines in vivo both in normal immune function and in disease.
The demonstration that the chemokine receptors, CCR5 and CXCR3 can act as co-receptors for the Human Immunodeficiency Virus and the finding that HIV cell tropism of primary virus isolates depends upon the chemokine receptors expressed by monocytes and T- cells serves to further emphasise the important role of chemokine.