2B4/CD244/SLAMF4 Products

Description

2B4, also known as CD244 and SLAMF4, is a type I transmembrane glycoprotein that is member of the signaling lymphocyte activation molecule (SLAM) subfamily in immunoglobulin (Ig) superfamily (1,2). The 2B4 protein plays a role in immune system associated diseases including the recognition and clearance of cancer cells, infected cells, and key allergy cells (1). 2B4 is expressed as a heterophilic receptor on the cell membrane of natural killer (NK) cells in addition to on monocytes and basophils, gamma/delta T cells, a subset of CD8+ T cells, and other immune cells and tissues (1). Additionally, 2B4 is considered a marker for CD8+ T cell exhaustion in chronic infection and increased expression has been observed in diseases including lymphocytic choriomeningitis virus (LCMV) and hepatitis B virus (HBV) (2). Human 2B4 protein is 370 amino acids (aa) in length with a theoretical molecular weight (MW) of 41 kDa (3). However, 2B4 contains multiple glycosylation sites that increases its observed MW to ~70 kDa (3). The 2B4/CD244 protein consists of a 21 aa signal peptide followed by an extracellular domain (ECD) with two Ig-like domains, a single transmembrane domain, and four cytoplasmic immunoreceptor tyrosine-based switch motifs (ITSMs) (3).

The 2B4 receptor has both activating and inhibitory signaling properties (1,4). 2B4's ligand is CD48, which is expressed on hematopoietic cells (4, 5). When bound to CD48, subsequent phosphorylation of the ITSMs occurs, followed by recruitment of SH-2-containing adaptor protein (SAP) and Fyn, leading to phosphorylation of PLCgamma and Vav1, and resulting in NK cell activation (4). In the absence of SAP, Src homology region 2-containing protein tyrosine phosphatases (SHP) get recruited and inhibits NK cell activation (4). In the context of infection such as Epstein-Barr virus (EBV), when lacking SAP, 2B4 has been shown to have an inhibitory function via impaired T cell cytotoxicity against EBV-infected cells (6). While 2B4 has a role in eliciting CD8+ T cell response, overexpression of 2B4 can lead to T cell exhaustion in states of chronic infection (6). Studies have suggested that the antibody blockade of the 2B4-CD48 interaction might enhance T cell and NK cell function, however given both the activating and inhibitory properties of the 2B4 receptor, more research needs to be done to prevent unwanted effects (6).

References

1. Buller CW, Mathew PA, Mathew SO. Roles of NK Cell Receptors 2B4 (CD244), CS1 (CD319), and LLT1 (CLEC2D) in Cancer. Cancers (Basel). 2020 Jul 1;12(7):1755. https://doi.org/10.3390/cancers12071755

2. Catakovic K, Klieser E, Neureiter D, Geisberger R. T cell exhaustion: from pathophysiological basics to tumor immunotherapy. Cell Commun Signal. 2017;15(1):1. https://doi.org/10.1186/s12964-016-0160-z

3. Uniprot (Q9BZW8)

4. Chen Y, Lu D, Churov A, Fu R. Research Progress on NK Cell Receptors and Their Signaling Pathways. Mediators Inflamm. 2020 Jul 24;2020:6437057. https://doi.org/10.1155/2020/6437057.

5. Pahima H, Puzzovio PG, Levi-Schaffer F. 2B4 and CD48: A powerful couple of the immune system. Clin Immunol. 2019 Jul;204:64-68. https://doi.org/10.1016/j.clim.2018.10.014.

6. Waggoner SN, Kumar V. Evolving role of 2B4/CD244 in T and NK cell responses during virus infection. Front Immunol. 2012;3:377. https://doi.org/10.3389/fimmu.2012.00377

Bioinformatics

Entrez	51744 Human
Uniprot	AAH53985 Human NM_016382 Human NP_057466 Human NP_057466.1 Human Q9BZW8 Human
Product By Gene ID	51744
Alternate Names	CD244 antigen CD244 molecule, natural killer cell receptor 2B4 h2B4 NAILNK cell activation-inducing ligand natural killer cell receptor 2B4 NKR2B4NK cell type I receptor protein 2B4,2B4CD244 natural killer cell receptor 2B4 Nmrk SLAMF4NK cell activation inducing ligand NAIL

Research Areas for 2B4/CD244/SLAMF4

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Phospho-Specific