B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator

John R. Sedy, Maya Gavrieli, Karen G. Potter, Michelle A. Hurchla, R. Coleman Lindsley, Kai Hildner, Stefanie Scheu, Klaus Pfeffer, Carl F. Ware, Theresa L. Murphy, Kenneth M. Murphy

Research output: Contribution to journalArticlepeer-review

489 Scopus citations

Abstract

B-and T lymphocyte attenuator (BTLA) provides an inhibitory signal to B and T cells. Previously, indirect observations suggested that B7x was a ligand for BTLA. Here we show that BTLA does not bind B7x; instead, we identify herpesvirus entry mediator (HVEM) as the unique BTLA ligand. BTLA bound the most membrane-distal cysteine-rich domain of HVEM, distinct from regions where the ligands LIGHT and lymphotoxin-α bound HVEM. HVEM induced BTLA tyrosine phosphorylation and association of the tyrosine phosphatase SHP-2 and repressed antigen-driven T cell proliferation, providing an example of reverse signaling to a non-tumor necrosis factor family ligand. The conservation of the BTLA-HVEM interaction between mouse and human suggests that this system is an important pathway regulating lymphocyte activation and/or homeostasis in the immune response.

Original languageEnglish
Pages (from-to)90-98
Number of pages9
JournalNature immunology
Volume6
Issue number1
DOIs
StatePublished - Jan 2005

Fingerprint

Dive into the research topics of 'B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator'. Together they form a unique fingerprint.

Cite this