Butyrophilin 3A1 (BTN3A1)/CD277

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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.

Butyrophilin 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.


  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.
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