Butyrophilin 3A1 (also called BTN3A1) is a 57 kDa type I transmembrane glycoprotein member of the Ig superfamily. It is expressed on a wide variety of immune cells. Similar to BTN3A2 and BTN3A3, BTN3A1 (484 amino acids) is composed of an extracellular N-terminal IgV and a membrane-proximal IgC domain followed by a transmembrane domain and a cytoplasmic tail. These Ig domains are also found in B7 family co-stimulatory molecules, suggesting structural and functional similarities between the two protein families (1). The intracellular portion of BTN3A1 contains a B30.2 domain (2). Although the B30.2 domain of BTN1A1 binds to xanthine oxidoreductase (XOR) and is conserved among BTN1A1 orthologs, this interaction with XOR is not shared by BTN3A1 (3). The B30.2 domain of butyrophilins also functions as a sensor for detecting changes in intracellular phopho-antigen (pAg) concentrations produced during tumorigenesis and microbial infections (4, 5). The specific binding of pAg by the B30.2 domain of BTN3A1 induces a conformational change in its ECD, leading to the activation of V gamma 9Vδ2 T cells (6). Thus, BTN3A1 acts as a critical protein for the activation of V gamma 9Vδ2 T cells following detection of distressed cells (7). The anti-tumor responses of V gamma 9Vδ2 T cells may be enhanced with agonistic anti-BTNA3 antibodies (8). No BTN3A1 homolog has yet been identified in rodents. However, Human BTN3A1 shares 92.4% and 91.6% sequence identity with baboon and rhesus monkey BTN3A1 respectively (9).