BTLA antibodies target the BTLA receptor, an immunoglobulin (Ig) superfamily member structurally analogous to PD-1 and CTLA-4. BTLA is expressed on immune cells such as B cells, T cells, macrophages, dendritic cells (DCs), and natural killer (NK) cells . Its primary role is to attenuate immune activation by binding to its ligand, herpesvirus entry mediator (HVEM), thereby regulating inflammation and tolerance .
BTLA is most abundant on B cells and CD4+ T cells, with lower expression on CD8+ T cells, macrophages, DCs, and NK cells . Naïve and anergic T cells show elevated BTLA levels, suggesting a role in maintaining immune quiescence .
BTLA antibodies modulate immune responses through:
Ligand Blockade: Anti-BTLA antibodies disrupt BTLA-HVEM interactions, enhancing T cell activation and cytokine production .
Signal Inhibition: BTLA engagement recruits SHP-1/SHP-2, suppressing NF-κB, NFAT, and AP-1 transcription factors, thereby reducing T cell proliferation .
Cis-Complex Formation: Co-expression of BTLA and HVEM on T cells promotes a naïve state, limiting differentiation .
Bacterial Infection: BTLA-deficient mice show accelerated Listeria monocytogenes clearance due to heightened proinflammatory cytokines (e.g., TNF-α, IL-12) .
Viral Infection: Cytomegalovirus (CMV) upregulates BTLA on CD8+ T cells, dampening antiviral responses .
Colitis and EAE: BTLA-KO mice exhibit exacerbated colitis and experimental autoimmune encephalomyelitis (EAE), highlighting its regulatory role .
Sepsis: Anti-BTLA antibodies increase peritoneal inflammation (e.g., TNF-α, IL-10) and mortality in septic mice .
Clone 8F4: A widely used anti-mouse BTLA antibody validated in flow cytometry and functional assays .
Suppliers: BioLegend (Cat #134803/134804) and R&D Systems (AF3007) offer BTLA antibodies for research .
Cancer Immunotherapy: BTLA blockade may synergize with anti-PD-1/CTLA-4 therapies to enhance antitumor immunity .
Autoimmune Diseases: Augmenting BTLA signaling could suppress pathogenic T cell responses .
While BTLA antibodies show promise, conflicting outcomes (e.g., proinflammatory effects in sepsis ) underscore context-dependent roles. Future work should explore: