Signaling lymphocytic activation molecule family member 4 (SLAMF4) (CD244)

Signaling lymphocytic activation molecule family member 4 (SLAMF4), also known as CD244 or 2B4, is a type-I transmembrane receptor belonging to the SLAM family and immunoglobulin superfamily[1][2][3]. It is expressed on all natural killer (NK) cells, a subset of T cells, monocytes, basophils, eosinophils, mast cells, and dendritic cells[3][4]. Its primary ligand is CD48, another member of the SLAM family[1][2][3]. CD244 contains extracellular Ig-like domains and a cytoplasmic tail bearing multiple immunoreceptor tyrosine-based switch motifs (ITSMs), permitting it to generate either activating or inhibitory signals depending on the intracellular adaptor proteins recruited, primarily SAP and EAT-2[1][2][4][7]. It plays a dual role in immune regulation by modulating NK and T cell responses in the context of infections, tumors, and immune surveillance. Dysregulation of CD244 signaling has been implicated in cancer immune evasion, chronic infections, and as a marker of functional exhaustion in tumor-infiltrating NK cells[2][4]. No therapeutic agents directly targeting CD244 are approved, but it remains an active area of research in cancer immunotherapy and immune modulation[2][6].

Other names

2B4Natural killer cell receptor 2B4NAIL (NK cell activation-inducing ligand)NKR2B4h2B4NK cell type I receptor protein 2B4SLAM family member 4Signaling lymphocytic activation molecule 4

Modulation of NK cell function via binding to CD48; Mediation of cytotoxicity or inhibition through interactions with SAP, EAT-2, and phosphatases such as SHP-1, SHP-2