BTLA Antibody

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Description

Introduction to BTLA Antibody

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 .

Expression Profile

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 .

Mechanisms of Action

BTLA antibodies modulate immune responses through:

  1. Ligand Blockade: Anti-BTLA antibodies disrupt BTLA-HVEM interactions, enhancing T cell activation and cytokine production .

  2. Signal Inhibition: BTLA engagement recruits SHP-1/SHP-2, suppressing NF-κB, NFAT, and AP-1 transcription factors, thereby reducing T cell proliferation .

  3. Cis-Complex Formation: Co-expression of BTLA and HVEM on T cells promotes a naïve state, limiting differentiation .

Infectious Disease

  • 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 .

Autoimmunity and Inflammation

  • 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 .

Table 2: Key Studies on BTLA Antibody Effects

Study FocusModel/SystemKey FindingsSource
Sepsis PathogenesisHem/CLP-induced sepsisAnti-BTLA ↑ cytokines, organ injury, mortality
T Cell ToleranceBTLA-KO MiceLoss of BTLA ↑ CD8+ memory T cell hyperreactivity
Innate ImmunityListeria InfectionBTLA deficiency ↑ bacterial clearance

Available Clones and Reagents

  • 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 .

Therapeutic Potential

  • 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 .

Challenges and Future Directions

While BTLA antibodies show promise, conflicting outcomes (e.g., proinflammatory effects in sepsis ) underscore context-dependent roles. Future work should explore:

  • Allelic variation impacts on antibody efficacy .

  • Combinatorial approaches with other checkpoint inhibitors .

Product Specs

Buffer
Liquid in PBS containing 50% glycerol, 0.5% BSA and 0.02% sodium azide.
Form
Liquid
Lead Time
Typically, we can ship the products within 1-3 business days after receiving your order. Delivery time may vary depending on the purchasing method or location. Please contact your local distributor for specific delivery time information.
Synonyms
B and T lymphocyte associated protein antibody; B and T lymphocyte attenuator antibody; B and T lymphocyte associated antibody; B- and T-lymphocyte attenuator antibody; B- and T-lymphocyte-associated protein antibody; BTLA antibody; BTLA_HUMAN antibody; BTLA1 antibody; CD272 antibody; CD272 antigen antibody; FLJ16065 antibody; MGC129743 antibody
Target Names
Uniprot No.

Target Background

Function
BTLA is an inhibitory receptor expressed on lymphocytes that negatively regulates antigen receptor signaling through PTPN6/SHP-1 and PTPN11/SHP-2. It may interact in cis (on the same cell) or in trans (on other cells) with TNFRSF14. In cis interactions, BTLA appears to play an immunoregulatory role, inhibiting in trans interactions in naive T cells to maintain a resting state. In trans interactions, BTLA can predominate during adaptive immune response, providing survival signals to effector T cells.
Gene References Into Functions
  1. Research indicates that both HVEM and UL144 bind to a common epitope of BTLA, regardless of whether engaged in trans or in cis. These studies were conducted using cell lines representing B-lymphocytes, T-lymphocytes, and natural killer cells. (HVEM = human herpes virus entry mediator; UL144 = membrane glycoprotein UL144 of Human herpesvirus 5; BTLA = human B- and T-lymphocyte attenuator) PMID: 29061848
  2. Our findings suggest that the BTLA/HVEM pathway contributes to peripheral T cell suppression in hepatocellular carcinoma patients. PMID: 30116751
  3. Our data provides the first evidence that increased BTLA predicts poor prognosis in patients with diffuse large B-cell lymphoma (DLBCL). Blockade of BTLA in conjunction with other checkpoints may represent a novel strategy for immunotherapy of DLBCL. PMID: 29353075
  4. Genetic variants of rs76844316 in BTLA influence the susceptibility to severe chronic hepatitis B and might play a protective role against the progression of chronic hepatitis B. PMID: 29558758
  5. The impairment of Bregs and CD19+/BTLA+ cells could play a significant pathogenic role in multiple sclerosis (MS). PMID: 27412504
  6. Our data demonstrates that BTLA acts as a molecule with the unique ability to provide both costimulatory and coinhibitory signals to activated CD8(+) T cells, resulting in extended survival, improved tumor control, and the development of a functional recall response. PMID: 28754817
  7. Results indicate that polymorphisms rs1982809 situated in the 3' UTR nearby region of the BTLA gene might be considered as a low-penetrating risk factor for RCC, but these results require further validation. PMID: 27234378
  8. The percentage of circulating BTLA+CD4+ lymphocytes was significantly higher in patients with severe community acquired pneumonia. PMID: 28164546
  9. Plasma concentrations of soluble BTLA were elevated early in sepsis/septic shock and correlated with disease severity. A baseline concentration greater than 21ng/mL was associated with a poor prognosis. PMID: 28056053
  10. This study shows that in chronic hepatitis B virus patients, a subset of inefficient interferon-gamma producing antigen-specific CD8+ T cells recruited to the liver expressed high BTLA levels. PMID: 27743606
  11. This study shows that BTLA expression is likely associated with positive rather than conventional negative regulation of CD11c antigen-presenting cell stimulatory capacity. PMID: 27717503
  12. rs1982809 BTLA gene polymorphism is associated with mRNA expression level and variations in the BTLA gene might be considered as a potentially low-penetrating chronic lymphocytic leukemia risk factor. PMID: 27933341
  13. A study demonstrated a decreased expression of BTLA in ocular Behcet's disease, suggesting that it may be involved in the development and recurrence of this disease. PMID: 26841832
  14. BTLA expression declines on B cells of the aged and is associated with low responsiveness to the trivalent influenza vaccine. PMID: 26277622
  15. Our study confirms that CD200/BTLA deletions are recurrent genetic lesions in the biology of BCP-ALL. PMID: 26137961
  16. Focal deletions of the BTLA were associated with B-cell precursor acute lymphoblastic leukemia. PMID: 25261097
  17. High BTLA expression levels in gastric cancer, identified by IHC, are an independent biomarker for poor prognosis in patients with gastric cancer. PMID: 25334051
  18. Data indicate that lung function and the expressions of B, T lymphocyte attenuator (BTLA) and Treg cells were lower in patients with rheumatism than those in normal controls. PMID: 24909289
  19. BTLA is a coreceptor that negatively regulates human Vgamma9Vdelta2 T-cell proliferation and plays a role in immune escape for lymphoma cells. PMID: 23692853
  20. BTLA and HVEM may have roles in graft rejection after kidney transplantation. PMID: 23375291
  21. BTLA regulates human B cell responses and has implications for future development of therapies modulating B cells. PMID: 22903545
  22. The expression of BTLA has been observed on the surface of several types of cells within synovial tissues of RA patients, indicating that this signal might be involved in the regulation of local T cell activation and the pathogenesis of RA. PMID: 22691359
  23. These findings support the role of BTLA and/or HVEM as potential, novel diagnostic markers of innate immune response/status and as therapeutic targets for sepsis. PMID: 22459947
  24. A study described the expression and spatial distribution of HVEM and BTLA in rheumatoid arthritis synovial tissues. Results indicated that HVEM/BTLA may be involved in regulating the progression of joint inflammation. PMID: 22179929
  25. BTLA-HVEM interactions impair minor histocompatibility antigen-specific T cell functionality, providing a rationale for BTLA signaling blockade in post-stem cell transplantation. PMID: 22634623
  26. When combined with PD-1 and Tim-3 blockades, BTLA blockade enhanced the expansion, proliferation, and cytokine production of NY-ESO-1-specific CD8(+) T cells. PMID: 22205715
  27. The HVEM-BTLA cis complex provides intrinsic regulation in T cells, serving as an interference mechanism that silences signals coming from the microenvironment. PMID: 21920726
  28. The results of a mutagenesis study of HVEM suggest that the CD160 binding region on HVEM was slightly different from, but overlapped with, the BTLA binding site. PMID: 21959263
  29. The 590C single-nucleotide polymorphism of B- and T-lymphocyte attenuator was significantly associated with susceptibility to rheumatoid arthritis, but not to systemic lupus erythematosus or Sjogren's syndrome. PMID: 21403914
  30. BTLA expression on overall CD4(+) and CD8(+) T cells was progressively decreased in HIV-1 infection, which was directly correlated with disease progression and CD4(+) T-cell differentiation and activation. PMID: 21592997
  31. In vitro blockade of the BTLA pathway augments both allogeneic and cytomegalovirus-specific CD8-positive T cell proliferation, thereby enhancing the functional capacity of cytotoxic T lymphocytes in viral infections. PMID: 20693422
  32. BTLA gene polymorphisms may affect the sporadic breast cancer risk and prognosis in Chinese women in northeast of Heilongjiang Province. PMID: 19585237
  33. Binding of HVEM to BTLA attenuates T cell activation, identifying HVEM/BTLA as a coinhibitory receptor pair. PMID: 15647361
  34. Distinct herpesviruses target the HVEM-BTLA cosignaling pathway, suggesting the importance of this pathway in regulating T cell activation during host defenses. PMID: 16131544
  35. The 2.8-A crystal structure of the BTLA-HVEM complex shows that BTLA binds to the N-terminal cysteine-rich domain of HVEM and employs a unique binding surface. PMID: 16169851
  36. BTLA is constitutively expressed on most CD4+ and CD8+ T cells and its expression progressively decreases upon T cell activation. PMID: 16643847
  37. Cross-linking of BTLA with mAb 7D7 suppressed T lymphocyte proliferation, downregulated the expression of T cell activation marker CD25, and inhibited the production of interferon (IFN)-gamma, interleukin (IL)-2, IL-4, and IL-10. PMID: 17257317
  38. BTLA is an inhibitory coreceptor of the B cell receptor (BCR) signaling pathway that attenuates B cell activation by targeting the downstream signaling molecules Syk and B cell linker protein (BLNK). PMID: 19155498
  39. This study did not find any genetic contribution of the BTLA gene to the development of T1D and SLE in the Japanese population. PMID: 19207938
  40. Results suggest that down-regulation of the BTLA-HVEM pathway may be involved in germinal center B-cell activation. PMID: 19762537
  41. The HVEM-BTLA cis-complex competitively inhibits HVEM activation by ligands expressed in the surrounding microenvironment, thus helping maintain T cells in the naive state. PMID: 19915044
  42. HVEM binds to B T lymphocyte attenuator (BTLA), an Ig family member, which inhibits T cell proliferation. PMID: 15568026

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Database Links

HGNC: 21087

OMIM: 607925

KEGG: hsa:151888

STRING: 9606.ENSP00000333919

UniGene: Hs.445162

Subcellular Location
Cell membrane; Single-pass type I membrane protein.

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