2B4 and CD48 are the main interactors in the Allergic Effector Unit (AEU), expressed by eosinophils and mast cells, respectively. The 2B4-CD48 high-affinity binding is conserved between species and higher than 2B4-CD2 binding, indicating the evolutionary significance of this interaction. The interaction between the two molecules is based on charged amino acids on 2B4, particularly Lys68 and Glu70, which are essential for CD48 mediated activation. The functional outcomes of CD48-2B4 binding can vary among different cell couples. For example, CD48 and 2B4 interaction on NK cells induce cell expansion and activation. Moreover, binding between 2B4 on NK cells and CD48 on T cells increases T cell proliferation. In addition, 2B4-CD48 binding on T cells results in T cell increased proliferation and cytotoxic activity.
Fig.1 2B4 and CD48 interaction in the allergic effector unit. (Pahima, 2019)
2B4 and CD48 Pathway in Drug Development
2B4 and CD48 interplay has been shown to have an important role in a multitude of cell-cell interactions. At the same time, 2B4 and CD48 have been demonstrated to have a prominent role in different human pathologies. Therefore, both receptors might become targets for therapy via mAbs or small molecules. According to the specific case, a possible strategy would involve either blockade or activation of one or both the two receptors. For example, homotypic interaction between 2B4 and CD4 on NK cells and T cells increases their cytotoxic activity against tumor cells, indicating that augmenting this pathway with an activating mAb toward 2B4 or CD48 might be a potential therapeutic approach. Moreover, the effectiveness of a blocking mAb against 2B4 in experimental sepsis or an activating anti-CD48 mAb in multiple myeloma (MM) has already been shown in vivo and in vitro. sCD48 being a decoy receptor for 2B4 and staphylococcal enterotoxin B (SEB), could also be used as a blocker of CD48 interactions with these entities.
Services at Creative Biolabs
Having focused on the immune checkpoint targeted drug development over the years, Creative Biolabs has established a comprehensive technology platform and become an industry-leading relevant service provider. We are now providing a series of quality-assured customer services for the 2B4 and CD48 pathway, including but not limited to: