BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1

Nat Immunol. 2003 Jul;4(7):670-9. doi: 10.1038/ni944. Epub 2003 Jun 8.

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).

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abatacept
  • Amino Acid Sequence
  • Animals
  • Antigens, CD
  • Antigens, Differentiation / physiology*
  • Antigens, Surface*
  • Apoptosis Regulatory Proteins
  • B7-1 Antigen / physiology
  • CTLA-4 Antigen
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Immunoconjugates*
  • Interleukin-2 / biosynthesis
  • Intracellular Signaling Peptides and Proteins
  • Lymphocyte Activation*
  • Mice
  • Molecular Sequence Data
  • Phosphorylation
  • Programmed Cell Death 1 Receptor
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases / physiology
  • Proteins / physiology*
  • RNA, Messenger / analysis
  • Receptors, Immunologic / chemistry
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / physiology*
  • T-Lymphocytes / immunology*

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • Antigens, Surface
  • Apoptosis Regulatory Proteins
  • B7-1 Antigen
  • CTLA-4 Antigen
  • Ctla4 protein, mouse
  • Immunoconjugates
  • Interleukin-2
  • Intracellular Signaling Peptides and Proteins
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor
  • Proteins
  • RNA, Messenger
  • Receptors, Immunologic
  • Abatacept
  • Protein Tyrosine Phosphatase, Non-Receptor Type 1
  • Protein Tyrosine Phosphatase, Non-Receptor Type 11
  • Protein Tyrosine Phosphatase, Non-Receptor Type 6
  • Protein Tyrosine Phosphatases
  • Ptpn11 protein, mouse
  • Ptpn6 protein, mouse

Associated data

  • GENBANK/AY293285
  • GENBANK/AY293286