2B4 / CD244 is a member of the signaling lymphocyte activation molecule (SLAM)-related receptor family and is also known as SLAMF4 and CD244. All members of the SLAM family share a similar structure, including an extracellular domain, a transmembrane region, and a tyrosine rich cytoplasmic region. Unlike most SLAM family members, 2B4 / CD244 does not bind via hemophilic interactions, but binds to CD48 / SLAMF2, which is broadly expressed by hematopoietic cells and functions as an adhesion and co-stimulatory receptor for both B and T cells. 2B4 & CD48 Immune Checkpoint Pathway can lead to signaling through both receptors. CD48 / SLAMF2 signaling in B cells leads to homotypic adhesion, proliferation and/or differentiation, release of inflammatory effector molecules and isotype class switching. In addition, all of these processes are also elicited in T cells via CD48 / SLAMF2 ligation with the addition of promoting their activation and/or cytotoxicity. 2B4 signaling requires signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) or EWS-activated transcript 2 (EAT-2; also called SH2D1B). In CD8 T cells and NK cells 2B4 / CD244 has been reported to exert both positive and negative regulation.
Sebastian Stark. 2B4 (CD244), NTB-A and CRACC (CS1) stimulate cytotoxicity but no proliferation in human NK cells. Int. Immunol. 2006 18 (2): 241-247.