Paired receptors

The siglec-like immunoglobulin domains of two paired receptors, PILRA (red) and PILRB (yellow), illustrating the similarities in structure between two ligand-binding domains of receptors with opposing signaling function. From PDB: 4NFC​ and PDB: 4NFB​.[1]

Paired receptors are pairs or clusters of receptor proteins that bind to extracellular ligands but have opposing activating and inhibitory signaling effects.[2][3][4] Traditionally, paired receptors are defined as homologous pairs with similar extracellular domains and different cytoplasmic regions, whose genes are located together in the genome as part of the same gene cluster and which evolved through gene duplication.[3][5] Homologous paired receptors often, but not always, have a shared ligand in common.[5][6] More broadly, pairs of receptors have been identified that exhibit paired functional behavior - responding to a shared ligand with opposing intracellular signals - but are not closely homologous or co-located in the genome.[4] Paired receptors are highly expressed in the cells of the immune system, especially natural killer (NK) and myeloid cells, and are involved in immune regulation.[5][7]

  1. ^ Lu, Q.; Lu, G.; Qi, J.; Wang, H.; Xuan, Y.; Wang, Q.; Li, Y.; Zhang, Y.; Zheng, C.; Fan, Z.; Yan, J.; Gao, G. F. (2014-06-03). "PILR and PILR have a siglec fold and provide the basis of binding to sialic acid". Proceedings of the National Academy of Sciences. 111 (22): 8221–8226. doi:10.1073/pnas.1320716111. PMC 4050567. PMID 24843130.
  2. ^ Lanier, Lewis L (June 2001). "Face off — the interplay between activating and inhibitory immune receptors". Current Opinion in Immunology. 13 (3): 326–331. doi:10.1016/S0952-7915(00)00222-3. PMID 11406364.
  3. ^ a b Kuroki, Kimiko; Furukawa, Atsushi; Maenaka, Katsumi (2012). "Molecular Recognition of Paired Receptors in the Immune System". Frontiers in Microbiology. 3: 429. doi:10.3389/fmicb.2012.00429. PMC 3533184. PMID 23293633.
  4. ^ a b Levi-Schaffer, Francesca; Mandelboim, Ofer (February 2018). "Inhibitory and Coactivating Receptors Recognising the Same Ligand: Immune Homeostasis Exploited by Pathogens and Tumours". Trends in Immunology. 39 (2): 112–122. doi:10.1016/j.it.2017.10.001. PMC 7106362. PMID 29066058.
  5. ^ a b c Akkaya, Munir; Barclay, A. Neil (February 2013). "How do pathogens drive the evolution of paired receptors?: HIGHLIGHTS". European Journal of Immunology. 43 (2): 303–313. doi:10.1002/eji.201242896. PMID 23280392. S2CID 677081.
  6. ^ Rumpret, Matevž; Drylewicz, Julia; Ackermans, Laura J. E.; Borghans, José A. M.; Medzhitov, Ruslan; Meyaard, Linde (December 2020). "Functional categories of immune inhibitory receptors". Nature Reviews Immunology. 20 (12): 771–780. doi:10.1038/s41577-020-0352-z. PMID 32612208. S2CID 220293404.
  7. ^ Martinet, Ludovic; Smyth, Mark J. (April 2015). "Balancing natural killer cell activation through paired receptors". Nature Reviews Immunology. 15 (4): 243–254. doi:10.1038/nri3799. PMID 25743219. S2CID 20825600.