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

Norihiko Watanabe; Maya Gavrieli; John R Sedy; Jianfei Yang; Francesca Fallarino; Susan K Loftin; Michelle A Hurchla; Natalie Zimmerman; Julia Sim; Xingxing Zang; Theresa L Murphy; John H Russell; James P Allison; Kenneth M Murphy

doi:10.1038/ni944

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.

Authors

Norihiko Watanabe¹, Maya Gavrieli, John R Sedy, Jianfei Yang, Francesca Fallarino, Susan K Loftin, Michelle A Hurchla, Natalie Zimmerman, Julia Sim, Xingxing Zang, Theresa L Murphy, John H Russell, James P Allison, Kenneth M Murphy

Affiliation

¹ Department of Pathology & Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, Box 8118, 660 South Euclid Avenue, St. Louis, Missouri 63110, USA.

PMID: 12796776
DOI: 10.1038/ni944

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