B and T lymphocyte attenuator (BTLA) is an immunoglobulin domain-containing glycoprotein whose expression is induced during T-cell activation. BTLA is similar to CTLA-4 and PD-1, all of which are coinhibitory receptors belonging to the CD28 family. However, unlike CTLA-4 and PD-1, BTLA does not interact with B7-Ig family counter receptors. Rather, the herpesvirus entry mediator (HVEM), a TNF receptor, acts as a molecular switch that modulates T-cell activation by propagating inhibitory signals through BTLA. The BTLAHVEM interaction is conserved between Mouse and human, suggesting that this system is an important pathway regulating lymphocyte activation.