Gene Symbol: 2B4
Description: CD244 natural killer cell receptor 2B4
Alias: 2B4, C9.1, F730046O15Rik, Ly90, NAIL, NKR2B4, Nmrk, SLAMF4, natural killer cell receptor 2B4, CD244 long isoform, CD244 short isoform, NK cell receptor 2B4, NK cell type I receptor protein 2B4, SLAM family member 4, non-MHC restricted killing associated, signaling lymphocytic activation molecule 4
Species: mouse
Products:     2B4

Top Publications

  1. Stepp S, Schatzle J, Bennett M, Kumar V, Mathew P. Gene structure of the murine NK cell receptor 2B4: presence of two alternatively spliced isoforms with distinct cytoplasmic domains. Eur J Immunol. 1999;29:2392-9 pubmed
    The NK cell receptor 2B4 is expressed on the surface of all murine NK cells and a subset of T cells. Ligation of 2B4 with monoclonal antibodies increases target cell lysis and IFN-gamma production...
  2. Chlewicki L, Velikovsky C, Balakrishnan V, Mariuzza R, Kumar V. Molecular basis of the dual functions of 2B4 (CD244). J Immunol. 2008;180:8159-67 pubmed
    b>2B4 belongs to the CD2 family of molecules and is expressed on all NK, gammadelta, and memory CD8(+) (alphabeta) T cells...
  3. Wang N, Calpe S, Westcott J, Castro W, Ma C, Engel P, et al. Cutting edge: The adapters EAT-2A and -2B are positive regulators of CD244- and CD84-dependent NK cell functions in the C57BL/6 mouse. J Immunol. 2010;185:5683-7 pubmed publisher
    ..Thus, as in humans, the EAT-2 adapters act as positive regulators of signaling lymphocyte activation molecule family receptor-specific NK cell functions in C57BL/6 mice. ..
  4. Kumaresan P, Stepp S, Bennett M, Kumar V, Mathew P. Molecular cloning of transmembrane and soluble forms of a novel rat natural killer cell receptor related to 2B4. Immunogenetics. 2000;51:306-13 pubmed
    ..One member of the IgSF, 2B4, is expressed on the surface of all mouse and human NK cells and the subset of T cells that mediate NK-like killing...
  5. Lee K, Bhawan S, Majima T, Wei H, Nishimura M, Yagita H, et al. Cutting edge: the NK cell receptor 2B4 augments antigen-specific T cell cytotoxicity through CD48 ligation on neighboring T cells. J Immunol. 2003;170:4881-5 pubmed
    b>2B4 is expressed on all NK and a subset of memory/effector CD8(+) T cells. 2B4 binds to CD48 and activates NK cytotoxicity, but its function on CD8(+) T cells is not clear...
  6. West E, Youngblood B, Tan W, Jin H, Araki K, Alexe G, et al. Tight regulation of memory CD8(+) T cells limits their effectiveness during sustained high viral load. Immunity. 2011;35:285-98 pubmed publisher
    ..memory cells was due to a block in sustaining cell proliferation, selective regulation by the inhibitory receptor 2B4, and increased reliance on CD4(+) T cell help...
  7. Brown D, Calpe S, Keszei M, Wang N, McArdel S, Terhorst C, et al. Cutting edge: an NK cell-independent role for Slamf4 in controlling humoral autoimmunity. J Immunol. 2011;187:21-5 pubmed publisher
    ..In this article, we demonstrate that a second member of the Slamf gene family, Slamf4 (Cd244), contributes to lupus-related autoimmunity. B6...
  8. Vaidya S, Stepp S, McNerney M, Lee J, Bennett M, Lee K, et al. Targeted disruption of the 2B4 gene in mice reveals an in vivo role of 2B4 (CD244) in the rejection of B16 melanoma cells. J Immunol. 2005;174:800-7 pubmed
    Murine 2B4 (CD244) is a cell surface receptor expressed on all NK cells, gammadelta-T cells, a subset of CD8(+) T cells, and all CD14(+) monocytes...
  9. Lee K, McNerney M, Stepp S, Mathew P, Schatzle J, Bennett M, et al. 2B4 acts as a non-major histocompatibility complex binding inhibitory receptor on mouse natural killer cells. J Exp Med. 2004;199:1245-54 pubmed
    ..b>2B4 (CD244) is expressed on all NK cells and the ligand for 2B4, CD48, is expressed on hematopoietic cells...

More Information


  1. Latchman Y, McKay P, Reiser H. Identification of the 2B4 molecule as a counter-receptor for CD48. J Immunol. 1998;161:5809-12 pubmed
    The CD48 molecule belongs to a subfamily of the Ig superfamily that also includes the CD2, CD58, 2B4, Signaling lymphocyte activation molecule (SLAM), and Ly-9 molecules...
  2. Orozco L, Cokus S, Ghazalpour A, Ingram Drake L, Wang S, Van Nas A, et al. Copy number variation influences gene expression and metabolic traits in mice. Hum Mol Genet. 2009;18:4118-29 pubmed publisher
    ..Our results suggest that CNVs have a significant impact on gene expression and that CNVs may be playing a role in the mechanisms underlying metabolic traits in mice. ..
  3. Morra M, Lu J, Poy F, Martin M, Sayos J, Calpe S, et al. Structural basis for the interaction of the free SH2 domain EAT-2 with SLAM receptors in hematopoietic cells. EMBO J. 2001;20:5840-52 pubmed
    ..We conclude that EAT-2 plays a role in controlling signal transduction through at least four receptors expressed on the surface of professional antigen-presenting cells. ..
  4. Boles K, Stepp S, Bennett M, Kumar V, Mathew P. 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. 2001;181:234-49 pubmed
    b>2B4 is a member of the CD2 subset of the immunoglobulin superfamily molecules expressed on natural killer (NK) cells and other leukocytes. It is the high affinity ligand for CD48...
  5. Waggoner S, Taniguchi R, Mathew P, Kumar V, Welsh R. Absence of mouse 2B4 promotes NK cell-mediated killing of activated CD8+ T cells, leading to prolonged viral persistence and altered pathogenesis. J Clin Invest. 2010;120:1925-38 pubmed publisher
    ..with inefficient T cell responses and sustained high-level expression of inhibitory receptors, such as the NK cell receptor 2B4 (also known as CD244), on virus-specific T cells...
  6. Kumaresan P, Huynh V, Mathew P. Polymorphism in the 2B4 gene of inbred mouse strains. Immunogenetics. 2000;51:758-61 pubmed
  7. Mathew P, Garni Wagner B, Land K, Takashima A, Stoneman E, Bennett M, et al. Cloning and characterization of the 2B4 gene encoding a molecule associated with non-MHC-restricted killing mediated by activated natural killer cells and T cells. J Immunol. 1993;151:5328-37 pubmed
    We have recently described a signal transducing molecule, 2B4, expressed on all NK and T cells that mediate non-MHC-restricted killing. The gene encoding this molecule was cloned and its nucleotide sequence determined...
  8. Boles K, Nakajima H, Colonna M, Chuang S, Stepp S, Bennett M, et al. Molecular characterization of a novel human natural killer cell receptor homologous to mouse 2B4. Tissue Antigens. 1999;54:27-34 pubmed
    ..However, we have previously described an activating receptor, 2B4, expressed on all murine NK cells and a subset of T cells that mediate non-major histocompatibility complex (MHC) ..
  9. Liu D, Krummey S, Badell I, Wagener M, Schneeweis L, Stetsko D, et al. 2B4 (CD244) induced by selective CD28 blockade functionally regulates allograft-specific CD8+ T cell responses. J Exp Med. 2014;211:297-311 pubmed publisher
    ..Here, we identified a critical role for the co-inhibitory SLAM family member 2B4 (CD244) in attenuating primary antigen-specific CD8(+) T cell responses in the presence of immune modulation with ..
  10. Chen C, Mittal R, Klingensmith N, Burd E, Terhorst C, Martin G, et al. Cutting Edge: 2B4-Mediated Coinhibition of CD4+ T Cells Underlies Mortality in Experimental Sepsis. J Immunol. 2017;199:1961-1966 pubmed publisher
    ..b>2B4 (CD244, SLAM4) is a cosignaling molecule expressed predominantly on NK cells and memory CD8+ T cells ..
  11. Moriggl R, Topham D, Teglund S, Sexl V, McKay C, Wang D, et al. Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells. Immunity. 1999;10:249-59 pubmed
    ..These phenotypes are not seen in mice lacking Stat5a or Stat5b alone. The results demonstrate that the Stat5 proteins, redundantly, are essential mediators of IL-2 signaling in T cells. ..
  12. Wahle J, Paraiso K, Kendig R, Lawrence H, Chen L, Wu J, et al. Inappropriate recruitment and activity by the Src homology region 2 domain-containing phosphatase 1 (SHP1) is responsible for receptor dominance in the SHIP-deficient NK cell. J Immunol. 2007;179:8009-15 pubmed
    ..This repertoire disruption is characterized by receptor dominance where inhibitory signals from 2B4 repress killing of complex targets expressing MHC class I and activating ligands...
  13. Georgoudaki A, Khodabandeh S, Puiac S, Persson C, Larsson M, Lind M, et al. CD244 is expressed on dendritic cells and regulates their functions. Immunol Cell Biol. 2015;93:581-90 pubmed publisher
    ..The SLAM receptor CD244 (2B4, SLAMf4) is expressed on a variety of immune cell types but most of its functions have been examined on NK and T cells...
  14. Cashman S, Lampe K, Sheridan R, Hoebe K. An ENU mutagenesis approach to dissect "self"-induced immune responses: Unraveling the genetic footprint of immunosurveillance. Oncoimmunology. 2012;1:856-862 pubmed
    ..a T'A amino acid substitution in the highly conserved third immuno-receptor tyrosine-based switch motif of CD244 (2B4)...
  15. Menner A, Rauch K, Aichele P, Pircher H, Schachtrup C, Schachtrup K. Id3 Controls Cell Death of 2B4+ Virus-Specific CD8+ T Cells in Chronic Viral Infection. J Immunol. 2015;195:2103-14 pubmed publisher
    ..Id3 (-) and Id3 (+) cells most prominently differed with regard to expression of the surface receptor 2B4; although Id3 (-) cells were 2B4(+), almost all Id3 (+) cells lacked expression of 2B4...
  16. Kubota K, Katoh H, Muguruma K, Koyama K. Characterization of a surface membrane molecule expressed by natural killer cells in most inbred mouse strains: monoclonal antibody C9.1 identifies an allelic form of the 2B4 antigen. Immunology. 1999;96:491-7 pubmed
    ..Furthermore, the strain distribution of the C9.1 antigen was shown to be antithetical to that of the 2B4 antigen already described as a molecule associated with major histocompatibility complex-unrestricted killing ..
  17. Assarsson E, Kambayashi T, Persson C, Chambers B, Ljunggren H. 2B4/CD48-mediated regulation of lymphocyte activation and function. J Immunol. 2005;175:2045-9 pubmed
    b>2B4 (CD244) is a member of the CD2 subset of the Ig superfamily. This molecule is expressed on innate immune cells, including NK cells, and on subsets of T cells...
  18. Clarkson N, Simmonds S, Puklavec M, Brown M. Direct and indirect interactions of the cytoplasmic region of CD244 (2B4) in mice and humans with FYN kinase. J Biol Chem. 2007;282:25385-94 pubmed
    Engagement of the receptor CD244 (2B4) by its ligand CD48 has inhibitory and activating potential, and this differs depending on experimental systems in mouse and human...
  19. Assarsson E, Kambayashi T, Schatzle J, Cramer S, von Bonin A, Jensen P, et al. NK cells stimulate proliferation of T and NK cells through 2B4/CD48 interactions. J Immunol. 2004;173:174-80 pubmed
    ..T cell activation and proliferation in response to CD3 cross-linking and specific Ag through interactions between 2B4 (CD244) on NK cells and CD48 on T cells...
  20. Dong K, Ge J, Gu S, Li S, Zhu W, Fan F, et al. Ox-LDL can enhance the interaction of mice natural killer cells and dendritic cells via the CD48-2B4 pathway. Heart Vessels. 2011;26:637-45 pubmed publisher
    ..Notably, we found that ox-LDL significantly promoted the interaction of NK cells and DCs via CD48-2B4 contact-dependent mechanisms...
  21. Fortenbery N, Paraiso K, Taniguchi M, Brooks C, Ibrahim L, Kerr W. SHIP influences signals from CD48 and MHC class I ligands that regulate NK cell homeostasis, effector function, and repertoire formation. J Immunol. 2010;184:5065-74 pubmed publisher
    Previously, we showed that 2B4 is a dominant inhibitory receptor in SHIP-deficient NK cells that prevents efficient cytolysis of complex targets...
  22. Lu Z, Di Domenico A, Wright S, Knight P, Whitelaw C, Pemberton A. Strain-specific copy number variation in the intelectin locus on the 129 mouse chromosome 1. BMC Genomics. 2011;12:110 pubmed publisher
    ..Since C57BL/6J mice possess only a single Itln gene, this is likely to contribute to functional differences between C57BL/6J and other mouse strains. ..
  23. Kim E, Kim N, Kim T, Kim K, Kim T, Kumar V, et al. Unidirectional signaling triggered through 2B4 (CD244), not CD48, in murine NK cells. J Leukoc Biol. 2010;88:707-14 pubmed publisher
    Engagement of 2B4 (CD244) with CD48 results in activation, costimulation, or inhibition of NK cell activities, depending on the cell types and the stage of differentiation...
  24. O Keeffe M, Song J, Liao G, De Calisto J, Halibozek P, Mora J, et al. SLAMF4 Is a Negative Regulator of Expansion of Cytotoxic Intraepithelial CD8+ T Cells That Maintains Homeostasis in the Small Intestine. Gastroenterology. 2015;148:991-1001.e4 pubmed publisher
    ..function of the mouse glycoprotein Signaling Lymphocyte Activation Molecule Family receptor (SLAMF) 4 (encoded by Slamf4) on the surface of CD8αβ αβ T-cell receptor (TCR)(+) IELs, and the roles of these cells in homeostasis ..
  25. Vaidya S, Mathew P. Of mice and men: different functions of the murine and human 2B4 (CD244) receptor on NK cells. Immunol Lett. 2006;105:180-4 pubmed
    b>2B4 was initially discovered on murine NK cells and T cells displaying non-MHC dependent cytotoxicity. Human 2B4 was cloned based on sequence homology with mouse 2B4...
  26. Clarkson N, Brown M. Inhibition and activation by CD244 depends on CD2 and phospholipase C-gamma1. J Biol Chem. 2009;284:24725-34 pubmed publisher
    ..We identify a novel signaling mechanism for CD244 through its potential to recruit phospholipase C-gamma1 via the conserved phosphorylated tyrosine motif in the tail of the adaptor protein EAT-2, which we show is important for function. ..
  27. Velikovsky C, Deng L, Chlewicki L, Fernández M, Kumar V, Mariuzza R. Structure of natural killer receptor 2B4 bound to CD48 reveals basis for heterophilic recognition in signaling lymphocyte activation molecule family. Immunity. 2007;27:572-84 pubmed
    ..Among the receptors regulating NK cell function is 2B4 (CD244), a member of the signaling lymphocyte-activation molecule (SLAM) family that binds CD48...
  28. Liu D, Suchard S, Nadler S, Ford M. Inhibition of Donor-Reactive CD8+ T Cell Responses by Selective CD28 Blockade Is Independent of Reduced ICOS Expression. PLoS ONE. 2015;10:e0130490 pubmed publisher
    ..Furthermore, we have previously published that 2B4 coinhibitory signals are functionally important for controlling graft-specific CD8+ T cell responses in mice ..
  29. Gao N, Schwartzberg P, Wilder J, Blazar B, Yuan D. B cell induction of IL-13 expression in NK cells: role of CD244 and SLAM-associated protein. J Immunol. 2006;176:2758-64 pubmed
    ..The induction of IL-13 mRNA by B cells may account for the effect of NK cells on the generation of Th2-type responses in the presence of some adjuvants. ..
  30. Taniguchi R, Guzior D, Kumar V. 2B4 inhibits NK-cell fratricide. Blood. 2007;110:2020-3 pubmed
    b>2B4 (CD244) and its ligand, CD48, are expressed on all natural killer (NK) cells...
  31. Lee K, Forman J, McNerney M, Stepp S, Kuppireddi S, Guzior D, et al. Requirement of homotypic NK-cell interactions through 2B4(CD244)/CD48 in the generation of NK effector functions. Blood. 2006;107:3181-8 pubmed
    b>2B4 belongs to the CD2 subset of the IgG family of receptors. Members in this family have been shown to function as coreceptors via homophilic or heterophilic interactions. Both 2B4 and CD2 bind to CD48, another member of this family...
  32. Johnson L, Vaidya S, Goldfarb R, Mathew P. 2B4(CD244)-mediated activation of NK cells reduces metastases of B16F10 melanoma in mice. Anticancer Res. 2003;23:3651-5 pubmed
    ..This killing is regulated by signals received through activating and inhibitory receptors. 2B4 (CD244), a member of the CD2 subset of Immunoglobulin superfamily, was identified as an activating receptor on NK ..
  33. Klem J, Verrett P, Kumar V, Schatzle J. 2B4 is constitutively associated with linker for the activation of T cells in glycolipid-enriched microdomains: properties required for 2B4 lytic function. J Immunol. 2002;169:55-62 pubmed
    b>2B4 is a receptor belonging to the Ig superfamily and is found on all murine NK cells as well as a small subset of T cells...
  34. Claus M, Meinke S, Bhat R, Watzl C. Regulation of NK cell activity by 2B4, NTB-A and CRACC. Front Biosci. 2008;13:956-65 pubmed
    b>2B4, NTB-A and CRACC are members of the recently defined family of SLAM-related receptors...
  35. Ray A, Yuan C, Miller N, Mei H, Dittel B. 2B4 Is Dispensable for T-Dependent B Cell Immune Responses, but Its Deficiency Leads to Enhanced T-Independent Responses Due to an Increase in Peritoneal Cavity B1b Cells. PLoS ONE. 2015;10:e0137314 pubmed publisher
    ..Herein, we evaluated whether the SLAM family member 2B4 (CD244) plays a role in immune cell development, homeostasis and antibody responses...
  36. Kiel M, Yilmaz O, Iwashita T, Yilmaz O, Terhorst C, Morrison S. SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells. Cell. 2005;121:1109-21 pubmed
    ..Many HSCs were associated with sinusoidal endothelium in spleen and bone marrow, though some HSCs were associated with endosteum. HSCs thus occupy multiple niches, including sinusoidal endothelium in diverse tissues. ..
  37. Kambayashi T, Assarsson E, Chambers B, Ljunggren H. Cutting edge: Regulation of CD8(+) T cell proliferation by 2B4/CD48 interactions. J Immunol. 2001;167:6706-10 pubmed
    The biological function of 2B4, a CD48-binding molecule expressed on T cells with an activation/memory phenotype, is not clear. In this report, we demonstrate that proliferation of CD8(+) T cells is regulated by 2B4...
  38. Gao N, Dang T, Dunnick W, Collins J, Blazar B, Yuan D. Receptors and counterreceptors involved in NK-B cell interactions. J Immunol. 2005;174:4113-9 pubmed
  39. Wandstrat A, Nguyen C, Limaye N, Chan A, Subramanian S, Tian X, et al. Association of extensive polymorphisms in the SLAM/CD2 gene cluster with murine lupus. Immunity. 2004;21:769-80 pubmed
    ..While autoimmunity may be mediated by a combination of genes in the SLAM/CD2 family cluster, the strongest candidate is Ly108, a specific isoform of which is constitutively upregulated in B6.Sle1b lymphocytes...
  40. Różycki B, Mioduszewski Å, Cieplak M. Unbinding and unfolding of adhesion protein complexes through stretching: interplay between shear and tensile mechanical clamps. Proteins. 2014;82:3144-53 pubmed publisher
    ..dynamics simulations, we analyze mechanically induced dissociation and unfolding of the protein complex CD48-2B4. This heterodimer is an indispensable component of the immunological system: 2B4 is a receptor on natural killer ..
  41. Chuang S, Lee Y, Stepp S, Kumaresan P, Mathew P. Molecular cloning and characterization of the promoter region of murine natural killer cell receptor 2B4. Biochim Biophys Acta. 1999;1447:244-50 pubmed
    ..We have previously identified, cloned and characterized a receptor, 2B4, expressed on murine NK cells...
  42. Elishmereni M, Fyhrquist N, Singh Gangwar R, Lehtimäki S, Alenius H, Levi Schaffer F. Complex 2B4 regulation of mast cells and eosinophils in murine allergic inflammation. J Invest Dermatol. 2014;134:2928-2937 pubmed publisher
    The cell surface molecule 2B4 (CD244) is an important regulator of lymphocyte activation, and its role in antiviral immunity and lymphoproliferative disorders is well established...
  43. Lee J, Lim S, Kim T, Kim K, Ng J, Kim Y, et al. NKG2D ligation relieves 2B4-mediated NK-cell self-tolerance in mice. Eur J Immunol. 2014;44:1802-13 pubmed publisher
    Along with MHC class I (MHCI), 2B4 provides nonredundant NK-cell inhibition in mice...
  44. Esteban L, Tsoutsman T, Jordan M, Roach D, Poulton L, Brooks A, et al. Genetic control of NKT cell numbers maps to major diabetes and lupus loci. J Immunol. 2003;171:2873-8 pubmed
    ..The second most significant locus (Nkt2) mapped to the same region as Idd13, a NOD-derived diabetes susceptibility gene on chromosome 2. ..
  45. Roncagalli R, Taylor J, Zhang S, Shi X, Chen R, Cruz Munoz M, et al. Negative regulation of natural killer cell function by EAT-2, a SAP-related adaptor. Nat Immunol. 2005;6:1002-10 pubmed
    ..Like SAP, EAT-2 was associated with the SLAM-related receptor 2B4 in NK cells. However, unlike SAP, EAT-2 was an inhibitor of NK cell function...
  46. Mooney J, Klem J, Wulfing C, Mijares L, Schwartzberg P, Bennett M, et al. The murine NK receptor 2B4 (CD244) exhibits inhibitory function independent of signaling lymphocytic activation molecule-associated protein expression. J Immunol. 2004;173:3953-61 pubmed
    b>2B4 (CD244) is a receptor belonging to the CD2-signaling lymphocytic activation molecule family and is found on all murine NK cells and a subset of NKT and CD8+ T cells...
  47. Zhao F, Cannons J, Dutta M, Griffiths G, Schwartzberg P. Positive and negative signaling through SLAM receptors regulate synapse organization and thresholds of cytolysis. Immunity. 2012;36:1003-16 pubmed publisher
    ..In the absence of SAP, signaling through the SLAM family members Ly108 and 2B4 resulted in increased recruitment of the SHP-1 phosphatase, associated with altered SHP-1 localization and ..
  48. Grant A, Gerard N, Brain S. Evidence of a role for NK1 and CGRP receptors in mediating neurogenic vasodilatation in the mouse ear. Br J Pharmacol. 2002;135:356-62 pubmed
    ..The results indicate that neurogenic vasodilatation can be measured in the mouse ear. The capsaicin-induced increased blood flow involves activation of, and possible interactions between, both NK(1) and CGRP(1) receptors. ..
  49. Wilson T, Presti R, Tassi I, Overton E, Cella M, Colonna M. FcRL6, a new ITIM-bearing receptor on cytolytic cells, is broadly expressed by lymphocytes following HIV-1 infection. Blood. 2007;109:3786-93 pubmed
  50. Tu C, Crumrine D, Man M, Chang W, Elalieh H, You M, et al. Ablation of the calcium-sensing receptor in keratinocytes impairs epidermal differentiation and barrier function. J Invest Dermatol. 2012;132:2350-2359 pubmed publisher
    ..3%) diet. Deleting CaR perturbs the epidermal Ca(2+) gradient and impairs keratinocyte differentiation and permeability barrier homeostasis, indicating a key role for the CaR in normal epidermal development...
  51. McNerney M, Guzior D, Kumar V. 2B4 (CD244)-CD48 interactions provide a novel MHC class I-independent system for NK-cell self-tolerance in mice. Blood. 2005;106:1337-40 pubmed
    ..Here, we show that 2B4 (CD244) and CD48 represent a second system for murine NK-cell self-recognition...