title: BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1.
abstract: During activation, T cells express receptors for receiving positive and negative costimulatory signals. Here we identify the B and T lymphocyte attenuator (BTLA), an immunoglobulin domain-containing glycoprotein with two immunoreceptor tyrosine-based inhibitory motifs. BTLA is not expressed by naive T cells, but it is induced during activation and remains expressed on T helper type 1 (T(H)1) but not T(H)2 cells. Crosslinking BTLA with antigen receptors induces its tyrosine phosphorylation and association with the Src homology domain 2 (SH2)-containing protein tyrosine phosphatases SHP-1 and SHP-2, and attenuates production of interleukin 2 (IL-2). BTLA-deficient T cells show increased proliferation, and BTLA-deficient mice have increased specific antibody responses and enhanced sensitivity to experimental autoimmune encephalomyelitis. B7x, a peripheral homolog of B7, is a ligand of BTLA. Thus, BTLA is a third inhibitory receptor on T lymphocytes with similarities to cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1).
authors.affiliation: Department of Pathology & Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, Box 8118, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Watanabe
authors.forename: Maya
authors.initials: M
authors.lastname: Gavrieli
authors.forename: John R
authors.initials: JR
authors.lastname: Sedy
authors.forename: Jianfei
authors.initials: J
authors.lastname: Yang
authors.forename: Francesca
authors.initials: F
authors.lastname: Fallarino
authors.forename: Susan K
authors.initials: SK
authors.lastname: Loftin
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Hurchla
authors.forename: Natalie
authors.initials: N
authors.lastname: Zimmerman
authors.forename: Julia
authors.initials: J
authors.lastname: Sim
authors.forename: Xingxing
authors.initials: X
authors.lastname: Zang
authors.forename: Theresa L
authors.initials: TL
authors.lastname: Murphy
authors.forename: John H
authors.initials: JH
authors.lastname: Russell
authors.forename: James P
authors.initials: JP
authors.lastname: Allison
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Murphy
mesh_terms: D000069594:Abatacept; D000595:Amino Acid Sequence; D000818:Animals; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000502:physiology*; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen / Q000502:physiology; D060908:CTLA-4 Antigen; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D018796:Immunoconjugates; D007376:Interleukin-2 / Q000096:biosynthesis; D047908:Intracellular Signaling Peptides and Proteins; D008213:Lymphocyte Activation; D051379:Mice; D008969:Molecular Sequence Data; D010766:Phosphorylation; D061026:Programmed Cell Death 1 Receptor; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases / Q000502:physiology; D011506:Proteins / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D015703:Antigens, CD; D000943:Antigens, Differentiation; D000954:Antigens, Surface; D051017:Apoptosis Regulatory Proteins; D018122:B7-1 Antigen; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007376:Interleukin-2; D047908:Intracellular Signaling Peptides and Proteins; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; D011506:Proteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D000069594:Abatacept; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053824:Protein Tyrosine Phosphatase, Non-Receptor Type 6; D017027:Protein Tyrosine Phosphatases; C516725:Ptpn11 protein, mouse; C509248:Ptpn6 protein, mouse