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
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Abatacept
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Amino Acid Sequence
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Animals
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Antigens, CD
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Antigens, Differentiation / physiology*
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Antigens, Surface*
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Apoptosis Regulatory Proteins
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B7-1 Antigen / physiology
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CTLA-4 Antigen
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Immunoconjugates*
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Interleukin-2 / biosynthesis
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Intracellular Signaling Peptides and Proteins
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Lymphocyte Activation*
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Mice
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Molecular Sequence Data
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Phosphorylation
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Programmed Cell Death 1 Receptor
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Protein Tyrosine Phosphatase, Non-Receptor Type 1
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases / physiology
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Proteins / physiology*
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RNA, Messenger / analysis
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Receptors, Immunologic / chemistry
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Receptors, Immunologic / genetics
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Receptors, Immunologic / physiology*
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T-Lymphocytes / immunology*
Substances
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Antigens, CD
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Antigens, Differentiation
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Antigens, Surface
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Apoptosis Regulatory Proteins
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B7-1 Antigen
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CTLA-4 Antigen
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Ctla4 protein, mouse
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Immunoconjugates
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Interleukin-2
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Intracellular Signaling Peptides and Proteins
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Pdcd1 protein, mouse
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Programmed Cell Death 1 Receptor
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Proteins
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RNA, Messenger
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Receptors, Immunologic
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Abatacept
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Protein Tyrosine Phosphatase, Non-Receptor Type 1
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Protein Tyrosine Phosphatase, Non-Receptor Type 11
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Protein Tyrosine Phosphatase, Non-Receptor Type 6
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Protein Tyrosine Phosphatases
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Ptpn11 protein, mouse
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Ptpn6 protein, mouse
Associated data
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GENBANK/AY293285
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GENBANK/AY293286