Molecular Classification
Receptor, Signaling lymphocytic activation molecule (SLAM) family, Immunoglobulin superfamily, Type-I transmembrane protein
Other Names
2B4, SLAM family member 4, SLAMF4, Natural killer cell receptor 2B4
Disease Roles
CancerInfection (especially viral, such as HIV, HBV, HCV)Autoimmune diseases

CD244 receptor Overview

CD244 (2B4, SLAMF4) is a type-I transmembrane protein receptor that belongs to the signaling lymphocytic activation molecule (SLAM) family and the immunoglobulin superfamily[1][2][4]. CD244 is predominantly expressed on natural killer (NK) cells, T cells (especially CD8+ subsets), monocytes, eosinophils, dendritic cells, and some myeloid cells[1][2][4]. Its primary ligand is CD48, a GPI-anchored molecule also belonging to the SLAM family, expressed on hematopoietic cells[1][5]. CD244 transmits either activating or inhibitory signals depending on the availability of intracellular adaptor proteins: the SH2-domain containing protein SAP (SLAM-associated protein) mediates activation, while other molecules such as EAT2 or phosphatases (SHP1/SHP2) mediate inhibitory effects[1][2][4][7]. The interaction of CD244 with CD48 regulates NK and T cell cytotoxicity, cytokine production, and the maintenance of memory and effector cell populations[4][6]. CD244 function is implicated in viral immunity, cancer immunosurveillance, and autoimmunity. Altered expression or signaling through CD244 can be associated with immune exhaustion, as seen in chronic viral infections and some malignancies[1][4][7]. The dual (activating/inhibitory) nature of CD244 makes it a complex but potentially valuable target for immunotherapy and as a disease biomarker[2][3][4][7].

Mechanism of Action

Modulation of immunity via activation or inhibition of NK and T cell responses through engagement with adaptor proteins (SAP, EAT2) and phosphatases Blockade or activation of CD244 to enhance or dampen immune cell cytotoxicity

Biological Functions

Immune response
Signal transduction
Regulation of natural killer (NK) cell cytotoxicity
Regulation of T cell activation and memory
Modulation of cell activation and inhibition

Disease Associations

Cancer
Infection (especially viral, such as HIV, HBV, HCV)
Autoimmune diseases
Inflammatory diseases

Safety Considerations

  • Risk of immunosuppression or unintended activation of immune responses if targeted therapeutically
  • Potential to disrupt normal immune homeostasis and tolerance

Interacting Drugs

None specifically approved as drugs, but CD244 is being explored as a therapeutic target and for antibody-based approaches in immunotherapy[4][7].

Associated Biomarkers

Biomarker
Expression level of CD244 on NK cells and T cells as a biomarker for immune exhaustion in chronic infections (e.g., HIV, HCV, HBV)[1][4][7]
Potential prognostic biomarker in cancer and autoimmune disease