Butyrophilins (BTNs) and butyrophilin like (BTNL) molecules are regulators of immune responses that belong to the immunoglobulin (Ig) superfamily of transmembrane proteins. They are structurally related to the B7 family of co-stimulatory molecules and have similar immunomodulatory functions (Afrache et al. 2012, Arnett & Viney 2014). BTNs are implicated in T cell development, activation and inhibition, as well as in the modulation of the interactions of T cells with antigen presenting cells and epithelial cells. Certain BTNsare genetically associated with autoimmune and inflammatory diseases (Abeler Domer et al. 2014).
The human butyrophilin family includes seven members that are subdivided into three subfamilies: BTN1, BTN2 and BTN3. The BTN1 subfamily contains only the prototypic single copy BTN1A1 gene, whereas the BTN2 and BTN3 subfamilies each contain three genes BTN2A1, BTN2A2 and BTN2A3, and BTN3A1, BTN3A2 and BTN3A3, respectively (note that BTN2A3 is a pseudogene). BTN1A1 has a crucial function in the secretion of lipids into milk (Ogg et al. 2004) and collectively, BTN2 and BTN3 proteins are cell surface transmembrane glycoproteins, that act as regulators of immune responses. BTNL proteins share considerable homology to the BTN family members. The human genome contains four BTNL genes: BTNL2, 3, 8 and 9 (Abeler Domer et al. 2014).