LAG‑3 is a new generation of immunotherapy targets and plays a balanced regulatory role in the human immune system. With advanced and high-end technologies, rich experienced scientists, Creative Biolabs is an excellent service provider in the field of tumor marker assay. After long years ahead to fully comprehend tumor markers, we launch our LAG-3 assay portfolio service which can be useful for targeted cancer therapy and diagnosis.
LAG-3, also known as CD223, is a member of the immunoglobulin superfamily. It is composed of a transmembrane region, an extracellular region and an intracellular region and has a molecular weight of 70 kDa. The gene of LAG-3 contains 8 exons, and the corresponding cDNA encodes a membrane protein, with 498 amino acids.
Fig.1 LAG-3 structure. (Shan, 2020)
The expression of LAG-3 is detected on activated CD4+ and CD8+ T cells, regulatory T cells (Tregs), a subpopulation of NK cells, B cells and plasmacytoid dendritic cells. In addition, LAG-3 is highly expressed in chronic virus infection and various tumors. It is involved in regulating the proliferation and activation of T lymphocytes and effector T lymphocytes, and plays a specific role in maintaining environmental stability in vivo. Overexpression of LAG-3 is also associated with autoimmune diseases, tumors and chronic toxic infectious diseases.
Galectin-3, a 31 kDa galactose-binding lectin, was found to interact with LAG-3 and inhibit the secretion of interferon-γ by CD8+ T cells in vitro, which regulates T cell activation and immunoprecipitation.
LSECtin is a member of the DC-SIGN family of molecules binding to the four glycosylated sites on LAG-3. It participates in a mechanism that LAG-3 can regulate CD8+ T cells and NK cell function in these environments.
α-synuclein fibrils, a protein aggregation, is a member of the Syn fibrils family. α-synuclein was found to bind to LAG-3, which leads to the intercellular delivery of pathological α-syn fibrils, while blocking their combination with a LAG-3 Ab could significantly reduce the toxicity and the intercellular delivery of pathological α-syn fibrils.
FGL1 was found to tightly bind to the LAG-3 receptor. When FGL1 binds to the LAG-3 receptor on the surface of T cells, T cell proliferation was inhibited and immune activity was also affected. Moreover, blocking the interaction between FGL1 and LAG-3 could enhance the antitumor effect of T lymphocytes, which has important significance in the research of tumor immunotherapy.
Researches have shown the role of LAG-3 in regulating the expansion of both CD4 and CD8 T cells and its role as a negative regulator. However, LAG-3 molecules lacking the KIEELE domain could not negatively modulate T cell function in vitro or in vivo.
Research has demonstrated that LAG-3-blocking antibody mitigates Treg function in vivo, and transfection of antigen-specific CD4 T cells with full-length, but not truncated, LAG-3 could confer in vitro regulatory properties.
Studies using LAG-3 knockout animals have confirmed the role for LAG-3 in regulating CD8 T cell homeostatic proliferation, as well as in the in vivo response to a superantigen.
Studies have shown that expression of a non-cleavable form of LAG-3 mediated an irreversible defect in T cell function, showing that LAG-3 cleavage was a major mechanism by which its negative regulatory function was mitigated.
Fig.2 LAG-3 signaling and the interplay with other immune checkpoints. (Long, 2020)
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