Abstract
The signaling lymphocytic activation molecule (SLAM) family of receptors is critically involved in the immune regulation of lymphocytes but has only been detected in mammals, with one member being present in Xenopus. Here, we describe the identification, cloning, and analysis of the chicken homologues to the mammalian SLAMF1 (CD150), SLAMF2 (CD48), and SLAMF4 (CD244, 2B4). Two additional chicken SLAM genes were identified and designated SLAMF3like and SLAM5like in order to stress that those two receptors have no clear mammalian counterpart but share some features with mammalian SLAMF3 and SLAMF5, respectively. Three of the chicken SLAM genes are located on chromosome 25, whereas two are currently not yet assigned. The mammalian and chicken receptors share a common structure with a V-like domain that lacks conserved cysteine residues and a C2-type Ig domain with four cysteines forming two disulfide bonds. Chicken SLAMF2, like its mammalian counterpart, lacks a transmembrane and cytoplasmic domain and thus represents a glycosyl-phosphatidyl-inositol-anchored protein. The cytoplasmic tails of SLAMF1 and SLAMF4 display two and four conserved immunoreceptor tyrosine-based switch motifs (ITSMs), respectively, whereas both chicken SLAMF3like and SLAMF5like have only a single ITSM. We have also identified the chicken homologues of the SLAM-associated protein family of adaptors (SAP), SAP and EAT-2. Chicken SAP shares about 70 % identity with mammalian SAP, and chicken EAT-2 is homologous to mouse EAT-2, whereas human EAT-2 is much shorter. The characterization of the chicken SLAM family of receptors and the SAP adaptors demonstrates the phylogenetic conservation of this family, in particular, its signaling capacities.
Similar content being viewed by others
Abbreviations
- GPI:
-
glycosyl-phosphatidyl-inositol
- SLAM:
-
signaling lymphocytic activation molecule
- SAP:
-
SLAM-associated protein family of adaptors
- ITSM:
-
immunoreceptor tyrosine-based switch motif
References
Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402
Bendtsen JD, Nielsen H, von Heijne G, Brunak S (2004) Improved prediction of signal peptides: SignalP 3.0. J Mol Biol 340:783–795
Boles KS, Stepp SE, Bennett M, Kumar V, Mathew PA (2001) 2B4 (CD244) and CS1: novel members of the CD2 subset of the immunoglobulin superfamily molecules expressed on natural killer cells and other leukocytes. Immunol Rev 181:234–249
Cannons JL, Tangye SG, Schwartzberg PL (2011) SLAM family receptors and SAP adaptors in immunity. Annu Rev Immunol 29:665–705
Colonna M (1997) Specificity and function of immunoglobulin superfamily NK cell inhibitory and stimulatory receptors. Immunol Rev 155:127–133
Daeron M, Jaeger S, Du Pasquier L, Vivier E (2008) Immunoreceptor tyrosine-based inhibition motifs: a quest in the past and future. Immunol Rev 224:11–43
Dong Z, Davidson D, Perez-Quintero LA, Kurosaki T, Swat W, Veillette A (2012) The adaptor SAP controls NK cell activation by regulating the enzymes Vav-1 and SHIP-1 and by enhancing conjugates with target cells. Immunity 36:974–985
Göbel TW, Bolliger L (1998) The chicken TCR ζ-chain restores the function of a mouse T cell hybridoma. J Immunol 160:1552–1554
Göbel TW, Chen CH, Cooper MD (1996a) Avian natural killer cells. Curr Top Microbiol Immunol 212:107–117
Göbel TW, Chen CH, Cooper MD (1996b) Expression of an avian CD6 candidate is restricted to αβ T cells, splenic CD8+ γδ T cells and embryonic natural killer cells. Eur J Immunol 26:1743–1747
Guselnikov SV, Laktionov PP, Najakshin AM, Baranov KO, Taranin AV (2011) Expansion and diversification of the signaling capabilities of the CD2/SLAM family in Xenopodinae amphibians. Immunogenet 63:679–689
Kageyama R, Cannons JL, Zhao F, Yusuf I, Lao C, Locci M, Schwartzberg PL, Crotty S (2012) The receptor Ly108 functions as a SAP adaptor-dependent on-off switch for T cell help to B cells and NKT cell development. Immunity 36:986–1002
Letunic I, Doerks T, Bork P (2012) SMART 7: recent updates to the protein domain annotation resource. Nucleic Acids Res 40:D302–D305
Long EO (1999) Regulation of immune responses through inhibitory receptors. Annu Rev Immunol 17:875–904
Neulen ML, Göbel TW (2012) Identification of a chicken CLEC-2 homologue, an activating C-type lectin expressed by thrombocytes. Immunogenet 64:389–397
Nimmerjahn F, Ravetch JV (2008) Fcgamma receptors as regulators of immune responses. Nat Rev Immunol 8:34–47
Odorizzi PM, Wherry EJ (2012) Inhibitory receptors on lymphocytes: insights from infections. J Immunol 188:2957–2965
Ravetch JV, Lanier LL (2000) Immune inhibitory receptors. Science 290:84–89
Reth M (1989) Antigen receptor tail clue. Nature 338:383–384
Rhee I, Veillette A (2012) Protein tyrosine phosphatases in lymphocyte activation and autoimmunity. Nat Immunol 13:439–447
Rogers SL, Viertlboeck BC, Göbel TW, Kaufman J (2008) Avian NK activities, cells and receptors. Semin Immunol 20:353–360
Schultz J, Milpetz F, Bork P, Ponting CP (1998) SMART, a simple modular architecture research tool: identification of signaling domains. Proc Natl Acad Sci U S A 95:5857–5864
Shlapatska LM, Mikhalap SV, Berdova AG, Zelensky OM, Yun TJ, Nichols KE, Clark EA, Sidorenko SP (2001) CD150 association with either the SH2-containing inositol phosphatase or the SH2-containing protein tyrosine phosphatase is regulated by the adaptor protein SH2D1A. J Immunol 166:5480–5487
Sidorenko SP, Clark EA (2003) The dual-function CD150 receptor subfamily: the viral attraction. Nat Immunol 4:19–24
Tamura K, Dudley J, Nei M, Kumar S (2007) MEGA4: Molecular Evolutionary Genetics Analysis (MEGA) software version 4.0. Mol Biol Evol 24:1596–1599
Veillette A (2010) SLAM-family receptors: immune regulators with or without SAP-family adaptors. Cold Spring Harb. Perspect Biol 2:1–15
Viertlboeck BC, Göbel TW (2007) Chicken thrombocytes express the CD51/CD61 integrin. Vet Immunol Immunopathol 119:137–141
Viertlboeck BC, Göbel TW (2011) The chicken leukocyte receptor cluster. Vet Immunol Immunopathol 144:1–10
Viertlboeck BC, Crooijmans RP, Groenen MA, Göbel TW (2004) Chicken Ig-like receptor B2, a member of a multigene family, is mainly expressed on B lymphocytes, recruits both Src homology 2 domain containing protein tyrosine phosphatase (SHP)-1 and SHP-2, and inhibits proliferation. J Immunol 173:7385–7393
Viertlboeck BC, Habermann FA, Schmitt R, Groenen MA, Du Pasquier L, Göbel TW (2005) The chicken leukocyte receptor complex: a highly diverse multigene family encoding at least six structurally distinct receptor types. J Immunol 175:385–393
Viertlboeck BC, Schmitt R, Göbel TW (2006) The chicken immunoregulatory receptor families SIRP, TREM, and CMRF35/CD300L. Immunogenet 58:180–190
Viertlboeck BC, Schweinsberg S, Hanczaruk MA, Schmitt R, Du Pasquier L, Herberg FW, Göbel TW (2007) The chicken leukocyte receptor complex encodes a primordial, activating, high-affinity IgY Fc receptor. Proc Natl Acad Sci U S A 104:11718–11723
Viertlboeck BC, Hanczaruk MA, Schmitt FC, Schmitt R, Göbel TW (2008) Characterization of the chicken CD200 receptor family. Mol Immunol 45:2097–2105
Viertlboeck BC, Schmitt R, Hanczaruk MA, Crooijmans RP, Groenen MA, Göbel TW (2009) A novel activating chicken IgY FcR is related to leukocyte receptor complex (LRC) genes but is located on a chromosomal region distinct from the LRC and FcR gene clusters. J Immunol 182:1533–1540
Zhao F, Cannons JL, Dutta M, Griffiths GM, Schwartzberg PL (2012) Positive and negative signaling through SLAM receptors regulate synapse organization and thresholds of cytolysis. Immunity 36:1003–1016
Zhu Y, Yao S, Chen L (2011) Cell surface signaling molecules in the control of immune responses: a tide model. Immunity 34:466–478
Acknowledgments
This study was supported by the Deutsche Forschungsgemeinschaft DFG GO489/5-1 grant.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Straub, C., Viertlboeck, B.C. & Göbel, T.W. The chicken SLAM family. Immunogenetics 65, 63–73 (2013). https://doi.org/10.1007/s00251-012-0657-6
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00251-012-0657-6