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CD244

Products

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All listed services and products are For Research Use Only. Do Not use in any diagnostic or therapeutic applications.

Background

CD244, also known as SLAMF4 or NAIL, is an approximately 40–70 kDa type I transmembrane glycoprotein that belongs to the signaling lymphocyte activation molecule (SLAM) family in the CD2 superfamily. CD244 is widely expressed on various hematopoietic cells, including NK, subsets of CD8+ cytotoxic T lymphocytes, γδ T cells as well as monocytes macrophages basophils eosinophils dendritic cells and myeloid-derived suppressor cell (MDSCs). CD48 is a GPI-anchored glycoprotein widely expressed on almost all hematopoietic cells. The CD244–CD48 interaction is one of the best characterized axes in SLAM receptor network, and serves as an important regulator of both innate and adaptive immune responses. In contrast to many immune receptors that function solely as activating or inhibitory molecules, CD244 displays striking functional plasticity—activation of lymphocytes can be either augmented by or inhibited via engagement with this receptor and is determined by other factors such as cellular context, differentiation stage, and intracellular availability of appropriate adapter proteins.

Fig.1 Structural characteristics of CD244. (OA Literature)Fig.1 Structural characteristics and signal transmission model of CD244.1

CD244 Protein Function: A Bidirectional Regulator of Immune Cell Activation

CD244 functional repertoire is focused on cancerous integration of activating/inhibitory signals by competitive adaptor recruitment:

  • NK Cell Cytotoxicity and Cytokine Production: On NK cells, the CD244 receptor provides a strong pathway of functional control in terms of cytotoxic activity. At high levels of SLAM-associated protein (SAP, SH2D1A), CD244 ligation attracts SAP to phosphorylated ITSMs and ultimately activates the Src-family kinase Fyn along with downstream effectors including Vav-1, PLCγ and LAT. This signaling cascade enhances NK cell degranulation and mucosal perforin secretion, as well as interferon-γ production. In contrast, in the absence of SAP (e.g., X-linked lymphoproliferative syndrome [XLP]) CD244 aggregates inhibitory phosphatases SHP-1, SHP-2 and also it binds to SIP; hence NK cells cytotoxicity is inhibited leading to hyporesponsive states. CD244 operates through this dual-mode, in which its intracellular SAP concentration determines the output of a molecular switch.
  • T-Cell Exhaustion and Dysfunction: Upregulation of CD244 on CD8+ T cells identifies an exhausted phenotype in the tumor microenvironment and during chronic viral infection. Continued CD48 engagement on tumor cells or antigen-presenting cells drives prolonged signaling via CD244, leading to suppression of T-cell proliferation and cytokine production within the context of low SAP levels and high phosphatase activity. The inhibitory function of CD244 has been reported for head and neck squamous cell carcinoma, chronic lymphocytic leukemia and multiple myeloma in which the blockade of this receptor reverses a state of exhaustion or dysfunction to restore effector T-cell functions that correlate with enhanced anti-tumor immunity.
  • Myeloid Cell Immunosuppression: This subtype of myeloid cells expressed CD244 in the microenvironment which resulted to immunosuppressive phenotypes (dendric cell and MDSCs). The CD244 signaling in DCs decreases the T-cell priming capacity and NK cell activation. Expression of CD244 in MDSCs correlates with an inhibition of antigen-specific, CD8+ T-cell responses. These observations have raised CD244 from a lymphocyte-limited receptor to an expansive myeloid checkpoint with wide-reaching potential in cancer immunotherapy.

CD244 Membrane Protein Product

Accelerate your research in Immunology and Immuno-Oncology with our catalogue of carefully manufactured recombinant CD244 membrane proteins. The IgV/IgC2 extracellular architecture, single-pass transmembrane topology and ITSM-dependent signaling of CD244 have all been identified as unique challenges for production. To tackle these challenges we utilize different expression platforms (mammalian HEK293 cells, insect cell systems and VLP formats) to yield correctly-folded, fully glycosylated CD244 constructs maintaining native CD48-binding affinity as well as SAP-recruitment competence. We provide membrane-bound, soluble extracellular domain fragments and variants of cytoplasmic tails for full-length CD244. All preparations are characterized biophysically to ensure they can be used for structural studies, ligand binding assays and antibody screening.

CD244 Protein Product

Not finding the membrane protein product you need? Contact us to start your one-stop custom service!

CD244 Stable Cell Line Product

Well-defined, reproducible cellular models are essential for analyzing CD244-mediated biology and therapeutic candidates. We specialize in stable cell lines expressing wild or engineered forms of mouse, and rat CD244 as well as regulated endogenous expression for loss-of-function studies. The platforms are designed for Low-access immune-oncology to high-throughput NK cell cytotoxicity assays, modeling CD8+ T-cell exhaustion and suppression assay of MDSC utilizing effective phenotype stimulations or blockade studies targeting CD48 with assurances of experimental consistency necessary to exploit the complexities generated by multi-phase areas in translational research.

CD244 Stable Cell Line Product

Not finding the stable cell line product you need? Contact us to start your one-stop custom service!

CD244 Recombinant Antibody Product

Our extensive portfolio of engineered high-affinity recombinant antibodies against CD244 in formats designed to withstand the rigors of most experimental protocols. These antibodies obtained by a state-of-the-art recombinant process demonstrate remarkable specificity, sensitivity and reproducibility as compared to conventional polyclonal antibodies. We offer a range of CD244 recombinant antibodies that have been validated for use in various applications, including WB, ELISA, FCM; IF IHC and ICC IP, allowing precise disclosure of CD244 detection and quantification from several sample types (e.g., NK cell lysates; TIL preparations & tissue sections) derived from cancer models.

CD244 Recombinant Antibody Product

Not finding the recombinant antibody product you need? Contact us to start your one-stop custom service!

Product Features

  • High Purity & Activity: High purity and verified integrity for dependable downstream work.
  • Diverse Expression Systems: Choice of expression formats to match routine or specialized projects.
  • Species Reactivity: Products available for human, mouse, pig, and other species.
  • Validated Applications: Application-tested to deliver consistent signals across common lab workflows.
  • Superior Batch-to-Batch Consistency: Stringent quality controls to ensure low variability from batch to batch.
  • Customization Options: Tags/Labels/package Modifications available upon request.

Custom CD244 Membrane Protein and Antibody Discovery Services

In addition to products in our catalog, we also provide custom services for membrane protein and antibody discovery & development. With some of the highest level expertise in SLAM family receptor biology and immune checkpoint pharmacology, we are equipped to help you with:

  • Production & Validation: Cloning of the synthesized optimized gene into an expression vector, plus small-scale expression trials to help determine the best expression conditions.
  • Custom Antibody Production: Produced via large-scale expression in mammalian/insect/cell culture or bacterial expression systems, purified in detergent or reconstituted into nanodiscs.
  • Engineered Cell Lines: Creation of stable cell lines that physiologically mimic endogenous CD244 expression and activity.
  • Functional Assessment Systems: Designing and executing assays to assess protein function and ligand binding.

Frequently Asked Questions (FAQ)

  1. Are your CD244 reagents approved for clinical diagnostic flow cytometry panels, natural killer cell subset enumeration or hematologic malignancy phenotyping?

    No, all reagents and services provided are for research purposes only and not intended to be used in diagnostic testing or therapeutic repair.

  2. Do you provide custom stable cell lines expressing CD244 and CD48 for modeling heterophilic adhesion and NK immune synapse-related processes?

    We can develop customized CD244/CD48 co-expression cell models according to specific research requirements. Cell model design, expression strategy, and appropriate readouts for receptor expression, cell–cell interaction, or synapse-related studies can be determined based on the intended experimental design.

  3. Do any of your CD244 antibodies show cross-reactivity with mouse and rat orthologs widely used in model systems for NK cell development or tumor immunology?

    Yes. The immunogen is directed towards a hyper-conserved region among mammalian species, allowing for consistent detection in human, mouse and rat lymphoid preparations without the need for numerous specific reagents from different sources.

  4. Do you offer stable cell lines with inducible CD244 expression or co-expression with SAP or CD48?

    Absolutely. We routinely generate Tetracycline-inducible systems and lines co-expressing CD244 with eitherCD48, SAP or EAT-2 reporter constructs for comprehensive pathway analysis. We welcome extensive conversations around your expression architecture and phenotypic needs.

Reference
  1. Sun, Lin, et al. "Advances in understanding the roles of CD244 (SLAMF4) in immune regulation and associated diseases." Frontiers in immunology 12 (2021): 648182. Under Open Access license CC BY 4.0, without modification. https://doi.org/10.3389/fimmu.2021.648182
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