The B and T lymphocyte attenuator (BTLA) is an Ig super family protein with an intermediate type Ig fold in the ectodomain and an ITIM inhibitory signaling domain in the cytosol. BTLA interacts with the herpesvirus entry mediator (HVEM; TNFRSF14), a TNFR super family member. Engagement of BTLA by HVEM, induces tyrosine phosphorylation of the ITIM motifs in the cytoplasmic tail of BTLA, allowing the recrui™ent of the phosphatases SHP-1 and SHP-2, which attenuate signaling.