CLR Ligands Rationally Design

C-type lectin receptors (CLRs) can recognize various carbohydrate motifs on the microorganism by the calcium-dependent manner. Creative Biolabs is a leader in the field of vaccine development and has focused on the cancer vaccines for years. The extensive experience and expertise of our scientists enable Creative Biolabs to provide innate immune stimulators related development services, especially CLR ligands rationally design.

C-type Lectin Receptors (CLRs)

C-type lectin receptors (CLRs), such as Dectin-1, Dectin-2, Mincle, CLEC9A, DC-SIGN, and MBL, comprise carbohydrate binding domain, through which various carbohydrate motifs on the microorganism are recognized in a calcium-dependent manner. CLRs contain a large family of receptors, whose lectin activity is mediated by conserved carbohydrate recognition domains.

  • Dectin-1. Dectin-1 is a specific receptor for β-glucan and can recognize several fungal species, including many human pathogens. Thus Dectin-1 plays an important role in host defense against these pathogens. Dectin-1 is composed of an extracellular carbohydrate recognition C-type lectin domain (CTLD) and a cytoplasmic tyrosine-containing domain similar to the immunoreceptor tyrosine-based activation motif.
  • Dectin-2. Dectin-2 binds to mannose carbohydrates such as mannose-capped lipoarabinomannan from mycobacteria and alpha-mannan found in Candida albicans. Dectin-2, which has a classical sugar-binding CTLD, is mainly expressed on tissue macrophages, dendritic cells, and inflammatory monocytes. Dectin-2 recognizes a variety of pathogens by identifying high mannose structures in a Ca2+-dependent manner.
  • Mincle. Macrophage-inducible C-type lectin (Mincle) is mainly expressed by activated macrophages and recognizes a variety of ligands such as damaged cells, yeast, fungus, and mycobacteria. Mincle has a single extracellular CTLD and a short cytoplasmic tail similar to Dectin-2.
  • CLEC9A (DNGR-1). CLEC9A (DNGR-1) has a limited expression pattern in dendritic cells and can be used for cancer treatment. CLEC9A binds to damaged or dead cells through exposed actin filaments and is considered a DAMP receptor.
  • DC-SIGN. DC-SIGN specifically recognizes several viruses (HIV-1, HCV, dengue virus, CMV, Ebola virus) and other microorganisms such as Leishmania and Candida. This type II transmembrane protein has a single C-type lectin domain and is expressed on immature monocyte-derived DCs. The pathogens have been shown to trigger DC-SIGN on human DCs to activate the serine and threonine kinase Raf-1, which subsequently leads to acetylation of the NF-κB subunit p65.
  • MBL. Mannose-binding lectin (MBL), a soluble C-type lectin, plays a key role in innate immunity against yeast via enhanced complement activation and enhanced polymorphonuclear uptake. MBL interacts with repetitive mannose and/or N-acetylglucosamine residue on the microorganism and carbohydrates on the glycoprotein (gp) 120 of HIV-1.

Recognition of mycobacterial pathogen-associated molecular patterns (PAMPs) by C-type lectin receptors (CLRs).

Fig.1 Recognition of mycobacterial pathogen-associated molecular patterns (PAMPs) by C-type lectin receptors (CLRs). (Marakalala MJ. 2017)

CLR Ligands

β-glucan, one of the well-studied Dectin-1 ligands, is the most abundant cell wall component of fungi and yeast. It was identified almost 40 years ago as potent immunomodulators that stimulated both innate and adaptive immunity. The ability of the innate immune system to rapidly identify and respond to invading pathogens is critical to controlling infection. β-glucan has been shown to have broad anti-infective and anti-tumor activity. In addition to activating the Dectin-1 signaling pathway, β-glucan can also improve the anti-tumor immune response by activating the complement system and recruiting tumor-killing granulocytes.

The uptake and subsequent actions of β-glucan on immune cells.

Fig.2 The uptake and subsequent actions of β-glucan on immune cells. (Chan GC. 2009)

Creative Biolabs is specialized in assisting clients with every stage of the vaccine development services, including adjuvant optimization. As an innovative and truly premier drug discovery and development research partner, Creative Biolabs is committed to providing the best quality services and high level of specialized support.

References

  1. Marakalala MJ, et al. Signaling C-type lectin receptors in antimycobacterial immunity. PLoS Pathog. 2017, 13(6): e1006333.
  2. Chan GC, et al. The effects of β-glucan on human immune and cancer cells. J Hematol Oncol. 2009, 2: 25.

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