Abstract
Paired receptors are groups of closely related membrane proteins that have the potential to either inhibit or activate. The CD200R family consists of one inhibitory member, CD200R and various numbers of activating genes according to species with three defined in C57BL/6 mice. A genomic PCR strategy was used to examine the repertoire of genes in both laboratory and wild-derived mice. Most mouse strains tested (18/22) had three activating genes, and 16 of these had either the combination of CD200RLa, Lb, and Lc or CD200RLa, Lb, and Le. The Lc and Le genes were mutually exclusive and were equally common (10 strains). Wild-derived mice varied more with one example of strains with one, two, and four activating genes. An inhibitory CD200R gene was detected in each mouse strain, although two slightly different sequences were found in both laboratory and wild-derived mice. This diversity is probably being driven by pathogens but is less extensive than for many NK paired receptors such as KIR and Ly49. It is possible that myeloid paired receptors are involved in immune regulation of responses against pathogens rather than directly killing infected cells as for NK cells and, hence, under less intense evolutionary pressure.
Similar content being viewed by others
References
Arase H, Mocarski ES, Campbell AE, Hill AB, Lanier LL (2002) Direct recognition of cytomegalovirus by activating and inhibitory NK cell receptors. Science 296:1323–1326
Barclay AN (2009) Signal regulatory protein alpha (SIRPalpha)/CD47 interaction and function. Curr Opin Immunol 21:47–52
Barclay AN, Brown MH (2006) The SIRP family of receptors and immune regulation. Nat Rev Immunol 6:457–464
Barclay AN, Hatherley D (2008) The counterbalance theory for evolution and function of paired receptors. Immunity 29:675–678
Cameron CM, Barrett JW, Liu L, Lucas AR, McFadden G (2005) Myxoma virus M141R expresses a viral CD200 (vOX-2) that is responsible for down-regulation of macrophage and T-cell activation in vivo. J Virol 79:6052–6067
Carlin AF, Uchiyama S, Chang YC, Lewis AL, Nizet V, Varki A (2009) Molecular mimicry of host sialylated glycans allows a bacterial pathogen to engage neutrophil Siglec-9 and dampen the innate immune response. Blood 113:3333–3336
Carlyle JR, Mesci A, Fine JH, Chen P, Belanger S, Tai LH, Makrigiannis AP (2008) Evolution of the Ly49 and Nkrp1 recognition systems. Semin Immunol 20:321–330
Cheng TP, French AR, Plougastel BF, Pingel JT, Orihuela MM, Buller ML, Yokoyama WM (2008) Ly49h is necessary for genetic resistance to murine cytomegalovirus. Immunogenetics 60:565–573
Fodil-Cornu N, Lee SH, Belanger S, Makrigiannis AP, Biron CA, Buller RM, Vidal SM (2008) Ly49h-deficient C57BL/6 mice: a new mouse cytomegalovirus-susceptible model remains resistant to unrelated pathogens controlled by the NK gene complex. J Immunol 181:6394–6405
Foster-Cuevas M, Wright GJ, Puklavec MJ, Brown MH, Barclay AN (2004) Human herpesvirus 8K14 protein mimics CD200 in down-regulating macrophage activation through CD200 receptor. J Virol 78:7667–7676
Hatherley D, Barclay AN (2004) The CD200 and CD200 receptor cell surface proteins interact through their N-terminal immunoglobulin-like domains. Eur J Immunol 34:1688–1694
Hatherley D, Cherwinski HM, Moshref M, Barclay AN (2005) Recombinant CD200 protein does not bind activating proteins closely related to CD200 receptor. J Immunol 175:2469–2474
Humphrey MB, Lanier LL, Nakamura MC (2005) Role of ITAM-containing adapter proteins and their receptors in the immune system and bone. Immunol Rev 208:50–65
Kaiser BK, Barahmand-Pour F, Paulsene W, Medley S, Geraghty DE, Strong RK (2005) Interactions between NKG2x immunoreceptors and HLA-E ligands display overlapping affinities and thermodynamics. J Immunol 174:2878–2884
Kojima T, Obata K, Mukai K, Sato S, Takai T, Minegishi Y, Karasuyama H (2007) Mast cells and basophils are selectively activated in vitro and in vivo through CD200R3 in an IgE-independent manner. J Immunol 179:7093–7100
Langlais CL, Jones JM, Estep RD, Wong SW (2006) Rhesus rhadinovirus R15 encodes a functional homologue of human CD200. J Virol 80:3098–3103
Lanier LL (2001) Face off–the interplay between activating and inhibitory immune receptors. Curr Opin Immunol 13:326–331
Mizushima S, Nagata S (1990) pEF-BOS, a powerful mammalian expression vector. Nucl Acids Res 18:5322
Nakayama M, Underhill DM, Petersen TW, Li B, Kitamura T, Takai T, Aderem A (2007) Paired Ig-like receptors bind to bacteria and shape TLR-mediated cytokine production. J Immunol 178:4250–4259
Parham P (2005) MHC class I molecules and KIRs in human history, health and survival. Nat Rev Immunol 5:201–214
Salata C, Curtarello M, Calistri A, Sartori E, Sette P, de Bernard M, Parolin C, Palu G (2009) vOX2 glycoprotein of human herpesvirus 8 modulates human primary macrophages activity. J Cell Physiol 219:698–706
Schmitter T, Agerer F, Peterson L, Munzner P, Hauck CR (2004) Granulocyte CEACAM3 is a phagocytic receptor of the innate immune system that mediates recognition and elimination of human-specific pathogens. J Exp Med 199:35–46
Smith HR, Heusel JW, Mehta IK, Kim S, Dorner BG, Naidenko OV, Iizuka K, Furukawa H, Beckman DL, Pingel JT, Scalzo AA, Fremont DH, Yokoyama WM (2002) Recognition of a virus-encoded ligand by a natural killer cell activation receptor. Proc Natl Acad Sci USA 99:8826–8831
Takenaka K, Prasolava TK, Wang JC, Mortin-Toth SM, Khalouei S, Gan OI, Dick JE, Danska JS (2007) Polymorphism in Sirpa modulates engraftment of human hematopoietic stem cells. Nat Immunol 8:1313–1323
Voehringer D, Rosen DB, Lanier LL, Locksley RM (2004) CD200 receptor family members represent novel DAP12-associated activating receptors on basophils and mast cells. J Biol Chem 279:54117–54123
Wright GJ, Cherwinski H, Foster-Cuevas M, Brooke G, Puklavec MJ, Bigler M, Song Y, Jenmalm M, Gorman D, McClanahan T, Liu MR, Brown MH, Sedgwick JD, Phillips JH, Barclay AN (2003) Characterization of the CD200 receptor family in mice and humans and their interactions with CD200. J Immunol 171:3034–3046
Yamada E, McVicar DW (2008) Paired receptor systems of the innate immune system. Curr Protoc Immunol Chapter 1: Appendix 1X
Zhang L, Stanford M, Liu J, Barrett C, Jiang L, Barclay AN, McFadden G (2009) Inhibition of macrophage activation by the myxoma virus M141 protein (vCD200). J Virol 83:9602–9607
Acknowledgements
We are grateful to Debbie Hatherley for advice on the CD200R family. This work was supported by the Medical Research Council grants (Ref. G0601169 and G0400808).
Author information
Authors and Affiliations
Corresponding author
Electronic supplementary material
Below is the link to the electronic supplementary material.
Supplementary Fig. 1
Screen for CD200RLa, Lb, Lc using alternative primers (outer set—see “Material and methods” and Fig. 1a). Selected mouse strains show similar patterns to those in Fig. 3.The numbers correspond to different mouse strains (Table 1), and the positions of the bands for the three genes are shown on the left L: 1 kb DNA ladder. Arrowheads indicate extra bands (PDF 172 kb)
Rights and permissions
About this article
Cite this article
Akkaya, M., Barclay, A.N. Heterogeneity in the CD200R paired receptor family. Immunogenetics 62, 15–22 (2010). https://doi.org/10.1007/s00251-009-0415-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00251-009-0415-6