The CD160, BTLA, LIGHT/HVEM pathway: a bidirectional switch regulating T-cell activation

Area of Science:

• Immunology
• Molecular Biology
• Cell Signaling

Background:

• Herpes virus entry mediator (HVEM) is a receptor expressed by T lymphocytes.
• HVEM ligands, including BTLA, LIGHT, and LTalpha, modulate T-cell activation.
• CD160 is a newly identified HVEM ligand involved in immune regulation.

Purpose of the Study:

• To investigate the role of CD160 as an HVEM ligand.
• To elucidate the mechanism by which HVEM ligands regulate T-cell activation.
• To explore the potential of targeting HVEM for therapeutic purposes.

Main Methods:

• Ligand binding assays to study interactions with HVEM.
• T-cell activation assays to assess functional consequences.
• Genetic manipulation of HVEM, including deletion or blockade of specific domains.

Main Results:

• CD160 binds to HVEM and delivers a coinhibitory signal, similar to BTLA.
• The cysteine-rich domain 1 (CRD1) of HVEM is crucial for binding coinhibitory ligands (CD160, BTLA) but not costimulatory ligands (LIGHT).
• Deletion or blockade of HVEM CRD1 converts HVEM into a dominant costimulatory molecule by preventing coinhibitory signaling.

Conclusions:

• HVEM functions as a bidirectional switch controlling T-cell activation based on the engaged ligand.
• Targeting HVEM CRD1 to block CD160 and BTLA binding offers a strategy to enhance immune responses.
• Therapeutic strategies are being developed to modulate HVEM signaling for improved vaccination and immune therapies.