Lectins and Their Role in Immune System

Lectins and Their Role in Immune System

What Are Lectins?

Lectins are sort of multivalent and complex proteins or glycan-binding proteins, the lectins family can bind a variety of carbohydrates reversibly and specifically. Lectins are involved in many biological processes including cell development, cell-cell interactions, signaling pathways, and immune responses. In innate immunity, lectins typically act as not only pattern recognition receptors (PRRs), recognizing pathogen-related molecular patterns (PAMPs) but also damage-related molecular patterns (DAMPs). C-type lectin receptors (CLRs), Siglecs, and galectins are the main classes of lectins in innate immunity, and selectins have similar properties to C-type lectins due to a related amino terminus and calcium-dependent binding.

Schematic representation of the overall structure of lectins from different sources.Fig.1 Schematic representation of the overall structure of lectins from different sources. (Sharon & Lis, 2013)

Carbohydrate Specificity

Generally, lectins are thought to have a molecular size between 60 and 400 kDa and have at least one non-catalytic domain that can bind to monosaccharides, oligosaccharides, and polysaccharides. It is also a conserved protein, which is widely present in plants, animals, and microorganisms forming monomeric, homotypic, and heterodimer molecules as well as homotypic and heterotetrameric molecules.

Lectins are classified into five specific groups based on the highest affinity they exhibit for monosaccharides: mannose, galactose/N-acetylgalactosamine, N-acetylglucosamine, fucose, and N-acetylneuraminic acid. Related to the biological function of lectins, these five are typical components of the sugars present on the surface of eukaryotic cells.

Structures of different lectins represented as ribbon diagrams.Fig.2 Structures of different lectins represented as ribbon diagrams. (Loris, 2002)

Roles in Immune System

Immunity to infection is mediated by two general systems: adaptive (or acquired) immunity and innate (or natural) immunity. The adaptive immune system includes both humoral and cell-mediated immunity and destroys invading pathogens. Innate immunity was previously thought to be a nonspecific immune response characterized by phagocytosis. However, innate immunity has considerable specificity and is able to distinguish between pathogens and normal cells. Lectins from plants and animals are commonly used in defense against pathogens and immune regulation. In animals, lectins serve as weapons against pathogens by aggregating and digesting them.

As talking before, based on lectins' ability to specifically recognize and bind carbohydrates, they play a role as recognition determinants in different biological processes. For the immune system, animal lectins play an important role in host defense against microorganisms. In addition, lectins play an important role in host defense against pathogens by activating antimicrobial autophagy and vacuoles. In viral infections, lectins are involved in binding and inhibiting the spread and replication of viruses. In some cases, bacterial lectins are responsible for attaching to sugar residues on phagocytes, allowing the latter to kill bacteria in the absence of serum factors, a process known as lectin phagocytosis. Due to lectins that can specifically bind to carbohydrates, it can be developed to research Antibody-Drug Conjugate (ADC).

Lectins Family

In the previous study, the animal lectins were divided into two main groups: the C-type (Ca2+-dependent) and S-type lectins (thiol-dependent). With increasing the number of described sequences, now animal lectins have at least 25 different types of fold, such as C-type, I-type, P-type, β-sandwich, calnexin/calreticulin, ERGIC-53, β-trefoil, cysteine-rich domain of C-type macrophage mannose receptor, fibrinogen-like domain, intelectins, and so on. Here we mainly talk about three different types of animal lectins: I-type, S-type, and C-type like lectin.

Applications

Due to lectins' great ability to recognize sugars with high specificity, they have been used as biotechnology tools by researchers. The main use of lectins is to detect, isolate and characterize sugar bindings in solution as well as within and on cells. Lectins, especially those from plants, are important tools for the detection, isolation, structure, and function study of complex carbohydrates, especially glycoproteins. Lectins can also be used as histochemical and cytochemical reagents for the detection of glycoconjugates on tissue sections and cells, as well as on subcellular organelles.

Lectins are also used to evaluate the cell surface and blood typing. As the agent, the change of test cells mitosis, sulfated glycoprotein hormones removal, control of glycoprotein biosynthesis, the interaction between cells - cells in the immune system, as well as a variety of infectious and autoimmune disease susceptibility and severity. In addition, a recent extension of lectin-based analytical tools is microarrays. CD BioGlyco provides a Microarray Platform including Glycan Microarray Assay and Lectin Microarray Assay for customers to study the interaction between carbohydrates and lectins.

CD BioGlyco has advanced platforms and services, especially our microarray assay platform. We provide customized experimental programs according to research needs, if you are interested in our services, please contact us for more detailed information.

References:

  1. Loris, R. Principles of structures of animal and plant lectins. Biochimica et Biophysica Acta (BBA) - General Subjects. 2002, 1572(2-3): 198–208.
  2. Sharon, N.; Lis, H. Lectins. Encyclopedia of Biological Chemistry. 2013, pp: 701–705.
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