CD48

Fig1. NK cell education in XLP1 as compared to healthy controls. (Raffaella Meazza, 2017)

What is CD48 protein?

CD48 (CD48 molecule) gene is a protein coding gene which situated on the long arm of chromosome 1 at locus 1q23. CD48 is a glycosylphosphatidylinositol-anchored protein belonging to the CD2 subfamily. It is expressed mainly on hematopoietic cells and exists in both membrane-associated and soluble forms. It is a low-affinity ligand for CD2 and is implicated as an important costimulatory molecule in lymphocyte activation. Indeed, CD48 has been described as facilitating cell adhesion, innate responses to bacterial infection, and graft rejection. In addition, CD48 is a high-affinity ligand for 2B4. The CD48 protein is consisted of 243 amino acids and its molecular mass is approximately 27.7 kDa.

What is the function of CD48 protein?

CD48, by binding to its ligand CD2, is involved in the recognition and activation of T cells, thus playing a key role in adaptive immune responses. Binding of CD48 to CD2 is also involved in the regulation of natural killer (NK) cells, influencing their mediated cytotoxic activities and thus also playing a role in the innate immune response. In interactions between lymphocytes, dendritic cells, macrophages, etc., CD48 helps transmit signals that guide cell migration and tissue localization, as well as subsequent immune responses. In some cases, CD48 may be involved in maintaining autoimmune tolerance, preventing the immune system from mistakenly attacking the body's tissues.

CD48 Related Signaling Pathway

The binding of CD48 to CD2 is one of the key steps in T cell activation. This process triggers a series of signaling events, including the activation of protein kinase C (PKC), the opening of calcium channels, and an increase in calcium ion concentration. These signals ultimately lead to the activation of transcription factors such as NF-kB and AP-1, which trigger changes in gene expression and regulation of cell function. In natural killer (NK) cells, the interaction of CD48 with CD2 can also regulate its recognition and killing activity against target cells. This process involves a variety of signaling molecules and pathways, such as SRC-family kinases and phosphatidylinositol 3-kinase (PI3K)/Akt pathway.

CD48 Related Diseases

CD48 plays a key role in the activation, proliferation and cytotoxicity of T and NK cells. Therefore, its abnormalities may be associated with autoimmune diseases, allergic reactions, and immune deficiencies. Abnormalities in CD48 may also be associated with other diseases, such as tumors, cardiovascular diseases, inflammatory diseases, and infectious diseases

Bioapplications of CD48

In some disease states, such as certain types of cancer and viral infections, the expression pattern of CD48 may change. Therefore, it can be used as a biomarker for these diseases. At the same time, monoclonal antibody therapy against CD48 is also being investigated for the treatment of certain blood diseases and solid tumors. Because of the important role of CD48 in immune response, it may also be involved in immune rejection after organ transplantation. Therefore, its study may help improve the success rate of transplantation.

Case Study 1: Katalin Kis-Toth, 2014

Signaling lymphocyte activation molecule family (SLAMF)2/CD48 is a coactivator and adhesion molecule on cells with hematopoietic origin. It ligates mainly SLAMF4 on effector/memory CD8(+) T cells and NK cells, suggesting a potential role during viral infection, with SLAMF2 acting as a ligand to activate SLAMF4-bearing cells. The ability of SLAMF2 to signal on its own after it is engaged and the functional consequences are largely unknown. The researchers found that cytosolic DNA-activated dendritic cells (DCs) upregulate the expression of SLAMF2 molecules. Using anti-SLAMF2 Ab and SLAMF4 recombinant protein, they found that SLAMF2 engagement activates immature DCs and, more interestingly, prolongs the survival of DNA-activated DCs by inhibiting IFN-β production and IFN-β-induced apoptosis and promotes the production of the granzyme B inhibitor protease inhibitor-9. Thus, SLAMF2 can serve as a survival molecule for DNA-activated DCs during their interaction with SLAMF4-expressing cytotoxic T cells. Based on these results, they propose that SLAMF2 engagement regulates adaptive immune responses by providing longer access of putative APCs to virus-specific effector T cells by prolonging the time frame of effective stimulation.

Fig1. Histograms show the distribution of SLAMF2 molecules on the surface of CD1a+ and CD1a− IDC and DNA-DC populations.

Fig2. SLAMF2 engagement rescues mature dendritic cells from cell death by inhibiting the production of IFNβ and the expression of caspase-4.

Case Study 2: Zhaowei Wang, 2021

A better understanding of the molecular mechanisms that manifest in the immunosuppressive tumor microenvironment (TME) is crucial for developing more efficacious immunotherapies for hepatocellular carcinoma (HCC), which has a poor response to current immunotherapies. Regulatory T (Treg) cells are key mediators of HCC-associated immunosuppression. The researchers investigated the selective mechanism exploited by HCC that lead to Treg cells expansion and to find more efficacious immunotherapies.

They used mass cytometry (CyTOF) and orthotopic cancer mouse models to analyze overall immunological changes after growth differentiation factor 15 (GDF15) gene ablation in HCC. They used flow cytometry, coimmunoprecipitation, RNA sequencing, mass spectrum, chromatin immunoprecipitation and Gdf15-/-, OT-I and GFP transgenic mice to demonstrate the effects of GDF15 on Treg cells and related molecular mechanism. The results showed GDF15 promotes the generation of peripherally derived inducible Treg (iTreg) cells and enhances the suppressive function of natural Treg (nTreg) cells by interacting with a previously unrecognized receptor CD48 on T cells and thus downregulates STUB1, an E3 ligase that mediates forkhead box P3 (FOXP3) protein degradation.

Fig3. Coimmunoprecipitation (CoIP) analysis of the interaction between GDF15 and CD48.

Fig4. The interaction of GDF15 with purified CD48, as measured by surface plasmon resonance (SPR) spectroscopy.

CD48 has several biochemical functions, for example, protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by CD48 itself. We selected most functions CD48 had, and list some proteins which have the same functions with CD48. You can find most of the proteins on our site.

CD48 has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with CD48 here. Most of them are supplied by our site. Hope this information will be useful for your research of CD48.

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