title: BTNL2, a butyrophilin-like molecule that functions to inhibit T cell activation.
abstract: B7 family members regulate T cell activation and tolerance. Although butyrophilin proteins share sequence homology with the B7 molecules, it is unclear whether they have any function in immune responses. In the present study, we characterize an MHC class II gene-linked butyrophilin family member, butyrophilin-like 2 (BTNL2), the mutation of which has been recently associated with the inflammatory autoimmune diseases sarcoidosis and myositis. Mouse BTNL2 is a type I transmembrane protein with two pairs of Ig-like domains separated by a heptad peptide sequence. BTNL2 mRNA is highly expressed in lymphoid tissues as well as in intestine. To characterize the function of BTNL2, we produced a BTNL2-Ig fusion protein. It recognized a putative receptor whose expression on B and T cells was significantly enhanced after activation. BTNL2-Ig inhibited T cell proliferation and TCR activation of NFAT, NF-kappaB, and AP-1 signaling pathways. BTNL2 is thus the first member of the butyrophilin family that regulates T cell activation, which has implications in immune diseases and immunotherapy.
authors.affiliation: Department of Immunology, University of Washington School of Medicine, Seattle, 98195, USA.
authors.forename: Thang
authors.initials: T
authors.lastname: Nguyen
authors.forename: Xikui K
authors.initials: XK
authors.lastname: Liu
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000071797:Butyrophilins; D006131:Growth Inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D007108:Immune Tolerance; D008213:Lymphocyte Activation / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: C408263:BTNL2 protein, human; C511667:BTNL2 protein, mouse; D000071797:Butyrophilins; D006131:Growth Inhibitors; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic