LAG-3 Antibody (17B4) [PE]

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Product Details

Summary
Reactivity Hu, PmSpecies Glossary
Applications Flow
Clone
17B4
Clonality
Monoclonal
Host
Mouse
Conjugate
PE

Order Details

LAG-3 Antibody (17B4) [PE] Summary

Immunogen
This LAG-3 Antibody (17B4) was prepared from synthetic peptide corresponding to 30 aa (GPPAAAPGHPLAPGPHPAAPSSWGPRPRRY) from the first N-terminal D1 domain of human LAG-3 (lymphocyte activation gene-3).
Specificity
LAG-3 Antibody (17B4) recognizes the 30 aa extra-loop of the first N-terminal D1 domain of human LAG-3.
Isotype
IgG1
Clonality
Monoclonal
Host
Mouse
Gene
LAG3
Purity
Protein A or G purified
Innovator's Reward
Test in a species/application not listed above to receive a full credit towards a future purchase.

Applications/Dilutions

Dilutions
  • Flow Cytometry
Application Notes
Optimal dilution of this antibody should be experimentally determined.
Theoretical MW
57.5 kDa.
Disclaimer note: The observed molecular weight of the protein may vary from the listed predicted molecular weight due to post translational modifications, post translation cleavages, relative charges, and other experimental factors.

Reactivity Notes

Primate reactivity reported in scientific literature (PMID: 32284611).

Packaging, Storage & Formulations

Storage
Store at 4C in the dark.
Buffer
PBS
Preservative
0.05% Sodium Azide
Purity
Protein A or G purified

Alternate Names for LAG-3 Antibody (17B4) [PE]

  • CD223 antigen
  • CD223
  • LAG3
  • LAG-3
  • lymphocyte activating 3
  • lymphocyte activation gene 3 protein
  • lymphocyte-activation gene 3
  • Secreted lymphocyte activation gene 3 protein
  • sLAG-3

Background

Lymphocyte activation gene-3 (LAG-3), also referred to as CD233, is a type I transmembrane protein with a theoretical molecular weight of 70 kDa that is a member of the immunoglobulin superfamily (IgSF) (1, 2). Human LAG-3 cDNA encodes 525 amino acids (aa) that includes a 28 aa signal sequence, a 422 aa extracellular domain (ECD) with four Ig-like domains (D1-D4), a transmembrane region and a highly charged cytoplasmic region. Within the ECD, human LAG-3 shares 70%, 67%, 76%, and 73% aa sequence identity with mouse, rat, porcine, and bovine LAG-3, respectively. The extracellular region of LAG-3 and the CD4 co-receptor share ~20% aa sequence homology but are structurally similar and both bind to major histocompatibility complex class II (MHCII) on antigen-presenting cells (APCs), although LAG-3 has much higher affinity (1, 3). LAG-3 is highly expressed in the lymph node, spleen, ovary, and appendix while expressed at a lower level in a variety of other tissues. More specifically, LAG-3 is expressed on activated CD4+ and CD8+ T cells, natural killer T (NKT) cells, natural killer (NK) cells, plasmacytoid dendritic cells (pDCs), and regulatory T cells (Tregs), but not on naive, or resting, T cells (1, 3).

As mentioned above, LAG-3 binds to MHCII and this occurs via a proline-rich amino acid loop in D1 (1, 3). Another unique feature of LAG-3 is the longer connecting peptide region between the D4 and the transmembrane, which is acted upon and cleaved by metalloproteinases a disintegrin and metallopeptidase domain (ADAM) 10 and ADAM17 to generate a soluble 54 kDa form of LAG-3 (sLAG-3) (1, 3). The interaction of LAG-3 with MHCII prevents the MHC molecule from binding to a T-cell receptor (TCR) or CD4, thereby functioning in an inhibitory role and suppressing the TCR signal (4). When LAG-3 crosslinks with the TCR/CD3 complex, it causes reduced T-cell proliferation and cytokine secretion (4). This negative regulation is important in controlling autoimmunity as one study found Lag3-/- NOD (non-obese diabetic) mice had accelerated diabetes onset and increased T-cell infiltration into islet cells (5). On the other hand, besides being a negative regulator of T-cells, LAG-3 binding to MHCII molecules on APCs induces dendritic cell maturation and cytokine secretion by monocytes (5, 6). In addition to MHCII, other reported ligands for LAG-3 includes fibrinogen-like protein 1 (FGL1), liver endothelial cell lectin (lSECtin), galectin-3 (Gal-3), and alpha-synuclein fibrils (1). Gal-3, for instance, is expressed on stromal cells and CD8+ T-cells in the tumor microenvironment and the interaction with LAG-3 was shown to be crucial for the suppression of secreted cytokine IFN-gamma and may control anti-tumor immune responses (1, 5). Interestingly, a mouse model of Parkinson's disease revealed LAG-3 binding to alpha-synuclein fibrils in the central nervous system, contributing to its pathogenesis (1, 5).

Recent cancer immunotherapeutic approaches have focused on inhibitory receptors such as LAG-3 to revive expression of cytotoxic T-cells to attack tumors (6). LAG-3 has been shown to be co-expressed and have synergy with another immune-checkpoint molecule called programmed-death 1 (PD-1) (1, 4, 5, 6). In a mouse model of colon adenocarcinoma LAG3 blockade alone was largely ineffective, however co-blockade of LAG-3 and PD-1 limited tumor growth and resulted in tumor clearance in 80% of mice, compared to 40% with PD-1 blockade alone (5). Additionally, in a model of fibrosarcoma the LAG-3/PD-1 duel blockade increased survival and the percentage of tumor-free mice (5). Analysis of a variety of human tumor samples (e.g. melanoma, colon cancer, head and neck squamous cell carcinoma) also suggest that LAG3 alone and combinatorial treatment with PD-1 may be a good target for treatment (1, 3-6). To date there are over 10 different agents targeting LAG-3 in clinical trials for cancer either as an anti-LAG-3 blocking antibody monotherapy or as a combination antagonist bispecific antibody, primarily with PD-1 (1, 3-6).

Alternative names for LAG-3 includes 17b4 lag3, 17b4 neutralizing, 17b4, CD223, FDC, LAG-3 17b4, LAG-3 blocking, and LAG3.

References

1. Maruhashi, T., Sugiura, D., Okazaki, I. M., & Okazaki, T. (2020). LAG-3: from molecular functions to clinical applications. Journal for Immunotherapy of Cancer, 8(2), e001014. https://doi.org/10.1136/jitc-2020-001014

2. Triebel, F., Jitsukawa, S., Baixeras, E., Roman-Roman, S., Genevee, C., Viegas-Pequignot, E., & Hercend, T. (1990). LAG-3, a novel lymphocyte activation gene closely related to CD4. The Journal of experimental medicine, 171(5), 1393-1405. https://doi.org/10.1084/jem.171.5.1393

3. Ruffo, E., Wu, R. C., Bruno, T. C., Workman, C. J., & Vignali, D. (2019). Lymphocyte-activation gene 3 (LAG3): The next immune checkpoint receptor. Seminars in immunology, 42, 101305. https://doi.org/10.1016/j.smim.2019.101305

4. Long, L., Zhang, X., Chen, F., Pan, Q., Phiphatwatchara, P., Zeng, Y., & Chen, H. (2018). The promising immune checkpoint LAG-3: from tumor microenvironment to cancer immunotherapy. Genes & cancer, 9(5-6), 176-189.

5. Andrews, L. P., Marciscano, A. E., Drake, C. G., & Vignali, D. A. (2017). LAG3 (CD223) as a cancer immunotherapy target. Immunological reviews, 276(1), 80-96. https://doi.org/10.1111/imr.12519

6. Goldberg, M. V., & Drake, C. G. (2011). LAG-3 in Cancer Immunotherapy. Current topics in microbiology and immunology, 344, 269-278. https://doi.org/10.1007/82_2010_114

Limitations

This product is for research use only and is not approved for use in humans or in clinical diagnosis. Primary Antibodies are guaranteed for 1 year from date of receipt.

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Secondary Antibodies

 

Isotype Controls

Other Available Formats

Alexa Fluor 350 NBP1-97657AF350
Alexa Fluor 405 NBP1-97657AF405
Alexa Fluor 488 NBP1-97657AF488
Alexa Fluor 532 NBP1-97657AF532
Alexa Fluor 594 NBP1-97657AF594
Alexa Fluor 647 NBP1-97657AF647
Alexa Fluor 700 NBP1-97657AF700
Alexa Fluor 750 NBP1-97657AF750
Allophycocyanin NBP1-97657APC
Allophycocyanin/Cy7 NBP1-97657APCCY7
Biotin NBP1-97657B
DyLight 350 NBP1-97657UV
DyLight 405 NBP1-97657V
DyLight 488 NBP1-97657G
DyLight 550 NBP1-97657R
DyLight 594 NBP1-97657DL594
DyLight 650 NBP1-97657C
DyLight 680 NBP1-97657FR
DyLight 755 NBP1-97657IR
FITC NBP1-97665
HRP NBP1-97657H
Janelia Fluor 549 NBP1-97657JF549
Janelia Fluor 646 NBP1-97657JF646
PE NBP1-97657PE
PE/Atto594 NBP1-97657PEATT594
PE/Cy5.5 NBP1-97657PECY55
PE/Cy7 NBP1-97657PECY7
PerCP NBP1-97657PCP

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Bioinformatics

Gene Symbol LAG3