anti-BTLA (human), mAb (6F4)

B and T lymphocyte associated (BTLA) is an Ig domain superfamily protein with cytoplasmic immunoreceptor tyrosine-based inhibitory motifs. The herpes virus entry mediator (HVEM), a member of the TNF receptor (TNFR) superfamily, can act as a molecular switch that modulates T cell activation by propagating positive signals from the TNF-related ligand LIGHT (TNFR superfamily 14), or inhibitory signals through the Ig superfamily member BTLA. The binding site on HVEM for BTLA is conserved in the orphan TNF receptor UL144, present in human CMV. UL144 binds BTLA, but not LIGHT, and inhibits T cell proliferation, selectively mimicking the inhibitory function of HVEM. BTLA also interacts with HVEM in cis, forming a heterodimeric complex in naive T cells that inhibits HVEM-dependent signaling. The cis-interaction between HVEM and BTLA is the predominant form expressed on the surface of naive human and mouse T cells and may be important to limit trans-signaling by LIGHT, BTLA, and CD160 that are expressed in adjacent activated cells.