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The CD160, BTLA, LIGHT/HVEM pathway: a bidirectional switch regulating T‐cell activation
Author(s) -
Cai Guifang,
Freeman Gordon J.
Publication year - 2009
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.2009.00783.x
Subject(s) - btla , lymphotoxin , mediator , microbiology and biotechnology , biology , t cell , immune system , immunology , chemistry
Summary: CD160 is a newly identified ligand for HVEM (herpes virus entry mediator). Previously identified HVEM ligands include BTLA (B‐ and T‐lymphocyte attenuator), LIGHT (lymphotoxin‐like, exhibits inducible expression, and competes with herpes simplex virus glycoprotein D for HVEM, a receptor expressed by T lymphocytes) and LTα (lymphotoxin‐α). The binding of LIGHT or LTα to HVEM delivers a costimulatory signal, whereas the binding of BTLA or CD160 to HVEM delivers a coinhibitory signal. Thus, HVEM is a bidirectional switch regulating T‐cell activation in a costimulatory or coinhibitory fashion whose outcome depends on the ligand engaged. The cysteine‐rich domain 1 (CRD1) of HVEM is essential for the binding of coinhibitory ligands CD160 and BTLA but not costimulatory ligand LIGHT. Deletion or blockade of HVEM CRD1 abolishes the binding of CD160 and BTLA, but not LIGHT, and converts HVEM to a dominant costimulatory molecule, possibly through the loss of negative signaling by CD160/BTLA. Therapies targeting the CRD1 of HVEM to block BTLA and CD160 binding are being developed to enhance immune responses and vaccination.