Butyrophilin-like 8 (BTNL8) is a member of the BTN/MOG Ig-superfamily and functions as a negative regulator of immune cell activation (1). Human BTNL8 is a 500 amino acid (aa) type I transmembrane glycoprotein that contains a signal peptide followed by an extracellular domain (ECD), a transmembrane region and a short cytoplasmic domain (2). The ECD of human BTNL8 shares 88% sequence identity with the ECD of mouse BTNL8. BTNL8 has two alternatively spliced forms: B7-like and BTN-like. Both isoforms of BTNL8 are expressed in a range of human tissues (3). The complete immunological function of BTNL molecules is only beginning to emerge. BTNL8 has been shown to be important in initiation of primary immune responses, suggesting a role in priming of naïve T lymphocytes (3). Down-regulation of BNTL8 mRNA levels has been associated with ulcerative colitis and colon cancer (4). BTNL8 are expressed in colon, lung, testis and neutrophils, and its expression is significantly decreased in ulcerative colitis, colonic tumors as compared to unaffected tissue (4). Soluble BTNL8-Fc fusion protein binds to resting, but not activated T cells. In vitro, BTNL8 co-stimulates T cell proliferation and cytokine production. In vivo injections of BTNL8-Fc significantly increases production of
Ag-specific IgG during the primary but not the secondary immune response (3).