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

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-alpha 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.
Mesh Terms:
Animals, Cell Line, Humans, Ligands, Lymphocyte Activation, Mice, Mice, Inbred BALB C, Receptors, Immunologic, Receptors, Tumor Necrosis Factor, Receptors, Tumor Necrosis Factor, Member 14, Receptors, Virus, Recombinant Fusion Proteins
Nat. Immunol.
Date: Jan. 01, 2005
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