Human Natural killer cell receptor 2B4(CD244) ELISA kit

Heterophilic receptor of the signaling lymphocytic activation molecule (SLAM) family; its ligand is CD48. SLAM receptors triggered by homo- or heterotypic cell-cell interactions are modulating the activation and differentiation of a wide variety of immune cells and thus are involved in the regulation and interconnection of both innate and adaptive immune response. Activities are controlled by presence or absence of small cytoplasmic adapter proteins, SH2D1A/SAP and/or SH2D1B/EAT-2. Acts as activating natural killer (NK) cell receptor. Activating function implicates association with SH2D1A and FYN. Downstreaming signaling involves predominantly VAV1, and, to a lesser degree, INPP5D/SHIP1 and CBL. Signal attenuation in the absence of SH2D1A is proposed to be dependent on INPP5D and to a lesser extent PTPN6/SHP-1 and PTPN11/SHP-2. Stimulates NK cell cytotoxicity, production of IFN-gamma and granule exocytosis. Optimal expansion and activation of NK cells seems to be dependent on the engagement of CD244 with CD48 expressed on neighboring NK cells. Acts as costimulator in NK activation by enhancing signals by other NK receptors such as NCR3 and NCR1. At early stages of NK cell differentiation may function as an inhibitory receptor possibly ensuring the self-tolerance of developing NK cells. Involved in the regulation of CD8(+) T-cell proliferation; expression on activated T-cells and binding to CD488 provides costimulatory-like function for neighboring T-cells. Inhibits inflammatory responses in dendritic cells (DCs).

1. Sole engagement of NKG2D, 2B4 or DNAM-1 is insufficient for NF-kappaB activation. PMID: 27221592
2. We determined a significantly lower expression of CD244 on monocytes in systemic lupus erythematosus patients compared to healthy controls. Furthermore, monocyte CD244 expression was negatively associated with several serum autoantibody titres. PMID: 28593610
3. SLAMF4 is a marker of intestinal immune cells which contributes to the protection against enteric pathogens and whose expression is dependent on the presence of the gut microbiota PMID: 28341747
4. The present study provides further insights into the role of the 2B4-CD48 interaction in the fine regulation of CD8(+) T-cell effector function upon antigenic stimulation. PMID: 26860368
5. Data show that 2B4 not only can bind to CD48 in trans but also interacts with CD48 in cis by using the same binding interface. Also, the results demonstrated that constitutive phosphorylation of 2B4 occurs only in the presence of CD48, and that cis binding is sufficient to induce substantial levels of baseline phosphorylation. PMID: 27249817
6. 2B4 expression is increased on CD4+ T cells in septic patients PMID: 28768726
7. Self-iNKR(-) NK cells in X-linked lymphoproliferative disease 1 patients are functional even in resting conditions, suggesting a role of the inhibitory 2B4/CD48 pathway in the education process during NK-cell maturation. PMID: 28386908
8. our results provide strong evidence that CD244 co-operates with c-Kit to regulate leukemogenesis through SHP-2/p27 signaling. PMID: 28126968
9. SLAMF4 gene and surface protein expression was down-regulated in CD8+ T cells from SLE patients compared with that in cells obtained from healthy donors. SLAMF4+ effector memory cells produced more granzyme B and perforin than SLAMF4- cells. PMID: 26314831
10. GSK-3 undergoes inhibitory phosphorylation at regulatory serine residues by the engagement of NKG2D and 2B4, either individually or in combination. PMID: 26022178
11. Cytomegalovirus-Induced Expression of CD244 after Liver Transplantation Is Associated with CD8+ T Cell Hyporesponsiveness to Alloantigen PMID: 26170387
12. CD8(+) T cells require 2B4 for Epstein-Barr virus-specific immune control, because 2B4 blockade after CD8(+) T-cell depletion did not further aggravate symptoms of the infection. PMID: 25722295
13. CD244 expression/signaling in tuberculosis correlates with high levels of a long noncoding RNA (lncRNA)-BC050410 [named as lncRNA-AS-GSTT1(1-72) or lncRNA-CD244] in the CD244(+)CD8(+) T-cell subpopulation. PMID: 26150504
14. show that in addition to NKG2D, human CEACAM1 can inhibit NK-cell activation via NKp30 or 2B4 PMID: 25824372
15. this study investigates the structural requirements for the recruitment of the human-activating NK-cell receptors NKG2D and 2B4 to detergent-resistant membrane fractions in the murine BA/F3 cell line and in the human NK-cell line NKL. PMID: 25545687
16. Study of SAP expression is specific but may have insufficient sensitivity for screening XLP1 as a single tool; however, combination with 2B4 functional assay allows identification of all cases PMID: 24985396
17. Blockade of 2B4/CD48 interaction resulted in improvement in function via perforin expression and degranulation as measured by CD107a surface mobilization on HTLV-1 specific CD8+ T cells. PMID: 24505299
18. In patients suffering from X-linked lymphoproliferative disease (XLP1), SAP is nonfunctional, not only abolishing the activating function of 2B4, but rendering this receptor inhibitory. PMID: 24659462
19. XLP1 inhibitory effect by 2B4 does not affect DNAM-1 and NKG2D activating pathways in NK cells. PMID: 24496997
20. Our results indicate that rapid CD244 internalization is induced by a two-signal mechanism and plays a role in modulation of antiviral CD8 T cell responses PMID: 23913963
21. data describe immune escape mechanism of monoclonal gammopathy/multiple myeloma occuring via downregulation of 3 major activating NK receptors (NCR3/NKp30, NKG2D and CD244/2B4/p38) in bone marrow, that was undetectable in peripheral blood. PMID: 23360454
22. Monocyte-induced natural killer cell dysfunction was markedly attenuated by blocking CD48 receptor 2B4 on NK cells, but not by blockade of NKG2D and NKp30. PMID: 23225218
23. TGF-beta1 may reduce the expression of NKG2D/DAP10 and 2B4/SAPin patients with hepatitis B. PMID: 22438812
24. These results identify a novel role for 2B4 molecules in eosinophil functional migratory response and may point to a novel tyrosine kinase-mediated ligation between CCR3 receptor and 2B4 co-receptor in eosinophil chemotaxis. PMID: 22230401
25. 2B4 is an important molecule within the network of costimulatory/inhibitory receptors regulating CD8+ T cell function in acute and chronic hepatitis C and 2B4 expression levels could also be a marker of CD8+ T cell dysfunction. PMID: 21625589
26. The results obtained through a cohort of European Caucasian Systemic sclerosis patients do not support the implication of CD244 gene in the pathogenesis of SSc but the gene were identified as Rheumatoid arthritis susceptibility gene. PMID: 21586211
27. glycosylation has an important impact on 2B4-mediated NK cell function and suggest that regulated changes in glycosylation during NK cell development and activation PMID: 21606496
28. These results suggest a potential physical association between 2B4 and the ITAM receptor complexes that is required for 2B4-initiated signaling and cell-mediated killing. PMID: 21439641
29. Data show that an increase in 2B4-expressing NK cells and a decrease in NKp46(+) NK cells occurred following intramuscular influenza vaccination. PMID: 21214542
30. Engagement of the activating natural killer (NK) cell receptor 2B4 rapidly mediates an increase in the force necessary to separate NK cells from tumor cells. PMID: 21270395
31. analysis of the importance of homotypic NK-to-NK cell cross-talk through 2B4/CD48 and CD2/CD58 pairs and further present their differential and overlapping roles in human NK cells PMID: 20813844
32. Single nucleotide polymorphisms of CD244 gene predispose to renal and neuro-psychiatric manifestations with systemic lupus erythematosus. PMID: 20437071
33. CD244 and PD-1 are highly coexpressed on virus-specific CD8+ T-cells in chronic HBV infection and blocking CD244 or its ligand CD48 may restore T-cell function independent of the PD-1 pathway. PMID: 21064032
34. Single nucleotide polymorphism in CD244 gene is associated with rheumatoid arthritis. PMID: 18794858
35. altered expression of splice variants of CS1 and 2B4 that mediate differential signalling in PBMC from patients with SLE. PMID: 20345977
36. Major histocompatibility class (MHC) I proteins expressed on natural killer (NK) cells inhibit NKR2B4 receptor self-killing not only by serving as an inhibitory ligand for inhibitory NK receptors but also through the association with 2B4. PMID: 20164429
37. Data show that pair-wise ligations of 2B4 with DNAM-1 and/or NKG2D lead to increased effector functions of primary CD4(+)CD28(-) T cells to suboptimal levels of anti-CD3 stimulation. PMID: 19904767
38. Up-regulation of the activatory receptor 2B4 by CD8+ alpha beta T cells in vivo correlates with the acquisition of effector cell properties such as granzyme B and perforin expression, IFN-gamma production, and down-regulation of chemokine receptor CCR7. PMID: 11714776
39. 2B4-mediated activation of natural killer cells involves the complex interactions of LAT, Ras, Raf, ERK and p38 kinase in the regulation of lytic function and cytokine production. PMID: 11714782
40. X-linked lymphoproliferative disease causes impaired 2b4 function in NK cells. PMID: 11774610
41. expressed on CD3+/CD56+ large granular lymphocytes proliferating in response to a tumor-expressed activating ligand (CD48) and killing autologous leukemia cells by a novel mechanism in a patient with acute myeloid leukemia. PMID: 11986947
42. Natural killer cell inhibitory receptors block actin cytoskeleton-dependent recruitment of 2B4 (CD244) to lipid rafts. PMID: 12515815
43. engagement of 2B4 on NK cells triggered a tyrosine phosphorylation signal PMID: 15169881
44. expression significantly up-regulated on CD4 and CD8 T cells during infectious mononucleosis, and significantly more lymphocytes expressing CD8 and CD244/CD8 in patients with severe sore throat. PMID: 15195244
45. The function of 2B4 as an adhesion molecule is underscored and a relevant role is suggested in the initial binding, scanning of target cells, and formation of cytotoxic natural killer cell immune synapse. PMID: 15356108
46. the SAP/2B4 pathway plays a key role in CTL lytic activity against EBV-positive targets by promoting the polarization of the lytic machinery PMID: 15677558
47. analysis of the molecular basis for the different signals generated by 2B4 PMID: 15713798
48. Functional analysis indicates that Lys-68 and Glu-70 in the extracellular domain of human 2B4 play a key role in the activation of human natural killer (NK) cells through 2B4/CD48 interaction. PMID: 16002700
49. Review of recent studies suggests an important role for interactions between 2B4 and CD48 in the course of T cell activation and proliferation PMID: 16081768
50. CD244-3BP2 association regulates cytolytic function but not IFN-gamma release PMID: 16177062

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Membrane; Single-pass type I membrane protein. Cell membrane.

Expressed in spleen, PBL, followed by lung, liver, testis and small intestine. Expressed in all natural killer (NK) cells, monocytes and basophils, TCR-gamma/delta+ T-cells, monocytes, basophils, and on a subset of CD8(+) T-cells.

HGNC: 18171

OMIM: 605554

KEGG: hsa:51744

STRING: 9606.ENSP00000357012

UniGene: Hs.157872