Butyrophilin 3A1 (BTN3A1)/CD277

What is BTN3A1?

Butyrophilin 3A1 (BTN3A1/CD277) is a 57 kDa type I glycoprotein that belongs to the B7 family. It is expressed on a wide variety of immune cells such as T and NK cells in humans and primates. Human BTN3A1 shares 92.4% and 91.6% sequence homology with rhesus monkey and baboon BTN3A1 respectively. There is no BTN3A1 homolog identified in rodents. The BTN3A1 protein has 484 amino acids and is composed of an extracellular N-terminal IgV and a membrane-proximal IgC domain followed by a transmembrane domain and a cytoplasmic tail. The intracellular portion of BTN3A1 contains a B30.2 domain which functions as a sensor to detect changes in intracellular phophoantigen (pAg). The specific binding of the B30.2 domain of BTN3A1 to pAg induces a conformational change in its extracellular domain, leading to activation of Vγ9Vδ2 T cells. Thus, BTN3A1 is considered a critical protein for the activation of Vγ9Vδ2 T cells and plays a role in the adaptive immune response. BTN3A1 can regulate the release of cytokines and IFNG by activated Vγ9Vδ2 cells and mediate the T cell responses toward infected and transformed cells characterized by high levels of phosphorylated metabolites.

Fig.1 Role of BTN3A1 in phosphoantigen presentation. (Kabelitz, 2014)

Role of BTN3A1 in Anti-tumor and Anti-infection Effect

Human BTN3A/CD277 has been proven to play an essential role in antitumor and anti-infection effects by regulating the γδ T-cell activation. BTN3A/CD277 is required for the PAg-induced activation of Vγ9Vδ2 T cells in both tumor and infectious contexts. The production of PAg is increased during tumorigenesis and microbial infections. The special binding of PAg and BTN3A/CD277 can induce Vγ9Vδ2 T-cell activation, promoting their cytokine production, thereby exerting anti-tumor and anti-infection activity. Interestingly, a study showed agonist anti-BTN3A mAbs might enhance antitumor responses of Vγ9Vδ2 T cells while antagonist anti-BTN3A mAbs might dampen the Vγ9Vδ2 T-cell responses to tumor cells. These suggest agonist and blocking BTN3A-specific antibodies that could be used for the immunotherapeutic modulation of Vγ9Vδ2 T-cell responses toward tumor or infected cells.

Creative Biolabs has focused on γδ T research for several years. Owing to the robust anti-tumor and anti-infection activity of certain γδ T cell subpopulations, they are expected to become promising tools for the treatment of tumors and infectious diseases. Our excellent experts are confident in offering a variety of solutions to support comprehensive γδ T cell research services, including the development of γδ T cell therapy, analysis of γδ T cell receptor, γδ T cell development, and γδ T cell engineering. If you are interested in these, please contact us for more details.

Reference

1. Kabelitz, Dieter. Critical role of butyrophilin 3A1 in presenting prenyl pyrophosphate antigens to human γδ T cells. Cellular & molecular immunology. 2014, 11(2): 117-119.