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

Research output: Contribution to journalArticle

559 Scopus citations

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 (TH1 but not TH2 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).

Original languageEnglish (US)
Pages (from-to)670-679
Number of pages10
JournalNature Immunology
Volume4
Issue number7
DOIs
StatePublished - Jul 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Watanabe, N., Gavrieli, M., Sedy, J. R., Yang, J., Fallarino, F., Loftin, S. K., Hurchla, M. A., Zimmerman, N., Sim, J., Zang, X., Murphy, T. L., Russell, J. H., Allison, J. P., & Murphy, K. M. (2003). BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1. Nature Immunology, 4(7), 670-679. https://doi.org/10.1038/ni944