HVEM/TNFRSF14 Protein, Human (HEK293, mFc)

HVEM/TNFRSF14, a receptor for four distinct ligands, intricately orchestrates a complex network of stimulatory and inhibitory signaling pathways. Ligands, including TNFSF14/LIGHT, homotrimeric LTA/lymphotoxin-alpha, and immunoglobulin superfamily members BTLA and CD160, collectively define this intricate signaling network. Operating through the TRAF2-TRAF3 E3 ligase pathway, HVEM/TNFRSF14 signals to promote immune cell survival and differentiation, playing a pivotal role in bidirectional cell-cell contact signaling between antigen-presenting cells and lymphocytes. Upon TNFSF14/LIGHT ligation, HVEM/TNFRSF14 delivers costimulatory signals to T cells, fostering cell proliferation and effector functions. Interactions with CD160 on NK cells enhance IFNG production and anti-tumor immune responses. In bacterial infections, HVEM/TNFRSF14 acts as a signaling receptor on epithelial cells for CD160 from intraepithelial lymphocytes, triggering the production of antimicrobial proteins and pro-inflammatory cytokines. Furthermore, HVEM/TNFRSF14, through binding CD160 on activated CD4+ T cells, down-regulates CD28 costimulatory signaling, restricting memory and alloantigen-specific immune responses. HVEM/TNFRSF14 exhibits both cis and trans interactions with BTLA, playing diverse roles in immune regulation and survival signaling during adaptive immune responses. Additionally, as a receptor for Herpes simplex virus 1/HHV-1, HVEM/TNFRSF14 is implicated in microbial infection.