2B4 is a member of the CD2 subset of the Ig superfamily expressed on all NK cells, T cells, a subset of CD8 T cells, and all human CD14 monocytes. It was originally identified as an activating receptor on murine NK cells and CD8 T cells that mediated non-MHC-restricted cytotoxicity. Ligation of surface 2B4 with anti-2B4 mAb augments the cytotoxicity of these cells against various tumor cell lines and induces IFN secretion. Similarly, murine T cells were shown to express 2B4, which played a functional role in the killing of skin cancers. In murine NK cells, 2B4 is expressed as two isoforms, 2B4-S and 2B4-L, that result from alternative splicing. Studies in which 2B4-S and 2B4-L were transfected into a rat leukemia cells line suggested that 2B4-S functions as an activating receptor, whereas 2B4-L is inhibitory. Other NK receptors have been shown to have a functionally opposite receptor, with both receptors binding to the same ligand. CD48 has been identified as the ligand for 2B4. Because CD48 is a common marker expressed by cells of the hemopoietic system, this suggests that 2B4 may play a role in immune regulation. Recent studies have elucidated the function of 2B4 on T cells. 2B4-CD48 interaction between neighboring CD8 T cells induces proliferation by acting as a costimulatory interaction. 2B4-CD48 interaction also augments the MHC-restricted killing by CD8 T cells and the natural cytotoxicity of NK cells.4 Thus, it appears that in mice 2B4 can regulate NK cells by two distinct mechanisms: by 2B4-CD48 interaction among NK cells and by interaction with CD48-expressing tumor cells. How these two are regulated in vivo is unknown. A recent study has shown that NK cells can also augment the proliferation of neighboring T cells through 2B4 on NK cells interacting with CD48 on T cells.
Vaidya S V, Stepp S E, McNerney M E, et al. Targeted disruption of the 2B4 gene in mice reveals an in vivo role of 2B4 (CD244) in the rejection of B16 melanoma cells[J]. The Journal of Immunology, 2005, 174(2): 800-807.