CLEC10A - C-type lectin domain containing 10A |Elisa - Clia - Antibody - Protein

Background

CLEC10A (C-type lectin domain containing 10A), also known as CD301 or MGL (Macrophage Galactose-Type Lectin), is a transmembrane protein in the C-type lectin receptor (CLR) family primarily expressed on antigen-presenting cells such as dendritic cells, macrophages, and certain monocytes. CLEC10A is part of the innate immune system, specializing in recognizing carbohydrate structures on the surfaces of cells and pathogens. Specifically, it binds to terminal galactose and N-acetylgalactosamine (GalNAc) residues, making it essential for identifying certain pathogens and interacting with glycoproteins on cellular surfaces.

CLEC10A’s specificity for galactose-containing glycans allows it to function in immune surveillance, pathogen clearance, and immunomodulation, making it a focal point in immune-related research. Its expression on dendritic cells and macrophages positions it to play a key role in the innate immune system's interactions with the adaptive immune response, particularly in tissue immune environments. CLEC10A’s involvement in recognizing glycosylated antigens has implications for disease processes, including infections, cancer, and autoimmune conditions.

Protein Structure

CLEC10A’s structure is optimized for its role in glycan recognition and immune cell signaling:

C-type Lectin Domain (CTLD):

• The C-type lectin domain is the core functional element of CLEC10A. This domain is responsible for binding to specific carbohydrate residues, namely terminal galactose and GalNAc. CLEC10A binds these sugars in a calcium-dependent manner, which stabilizes the carbohydrate-binding pocket within the lectin domain. This binding specificity is critical for CLEC10A’s ability to recognize pathogens and glycosylated antigens on cell surfaces.
• Structural studies indicate that the CTLD of CLEC10A has conserved carbohydrate-recognition motifs that enable selective binding to terminal sugars, a function central to its role in pathogen recognition and immune response regulation.

Extracellular Stalk Region:

• Preceding the CTLD is a stalk-like extracellular region that supports the positioning of the lectin domain. This stalk domain creates space between the cell membrane and the CTLD, facilitating CLEC10A’s access to glycan targets on larger proteins or cell surfaces.

Transmembrane Domain:

• CLEC10A has a single transmembrane domain that anchors it in the plasma membrane. This hydrophobic domain not only secures CLEC10A in place but also helps localize it within membrane microdomains, where it can efficiently interact with other immune receptors and participate in signaling cascades.

Cytoplasmic Tail:

• The cytoplasmic tail of CLEC10A contains potential signaling motifs, although they are not as well-characterized as those in other signaling receptors. This tail is hypothesized to interact with intracellular signaling pathways upon ligand binding, suggesting it might play a role in modulating immune responses or endocytosis.

Classification and Subtypes

CLEC10A is a member of the C-type lectin receptor family and is classified within group II of the C-type lectins, which are typically transmembrane proteins involved in immune functions. It shares structural similarity with other C-type lectins but is unique in its specificity for GalNAc and terminal galactose residues. This specificity distinguishes it from other lectins, such as DC-SIGN and CLEC4M (L-SIGN), which bind different carbohydrate structures. CLEC10A does not have defined subtypes; however, its functions may be modulated through interactions with various co-receptors or other cell-surface proteins in tissue-specific immune environments.

Function and Biological Significance

CLEC10A has a distinct role in immune recognition and modulation due to its unique glycan specificity:

Glycan Recognition and Pathogen Binding:

• CLEC10A’s ability to bind to terminal galactose and GalNAc residues allows it to recognize a variety of pathogen-associated molecular patterns (PAMPs). For instance, certain bacteria, fungi, and viruses display glycoproteins with terminal galactose residues, which CLEC10A can bind, initiating immune responses. This glycan recognition capability situates CLEC10A as a key player in early pathogen detection by dendritic cells and macrophages, cells crucial to the innate immune response.

Endocytosis and Antigen Processing:

• After binding its ligands, CLEC10A can mediate endocytosis, internalizing pathogens or glycoproteins for degradation and subsequent antigen processing. This process is critical for antigen-presenting cells to process and present pathogen-derived antigens on major histocompatibility complex (MHC) molecules, which is essential for activating T cells and linking the innate and adaptive immune responses.

Immune Regulation and Tolerance:

• CLEC10A’s interactions with glycan-bearing self-antigens are thought to contribute to immune tolerance, potentially preventing overactive immune responses. By binding to self-glycoproteins, CLEC10A may play a role in maintaining immune homeostasis and avoiding autoreactivity, which is particularly important in tissues rich in macrophages, such as the liver.

Role in Cancer:

• CLEC10A’s ability to recognize glycan structures on tumor cells is a growing area of research. Tumor cells often express abnormal glycosylation patterns, and CLEC10A can bind these atypical glycans. This binding has implications for tumor immune surveillance, as it may facilitate immune recognition of cancer cells or contribute to immune evasion mechanisms in the tumor microenvironment.

Clinical Issues

CLEC10A has been linked to several clinical conditions, given its role in immune surveillance and glycan recognition:

Infectious Diseases:

• Due to its ability to bind specific glycan residues on pathogens, CLEC10A plays a role in various infectious diseases. Its interactions with bacterial and viral glycoproteins may facilitate pathogen clearance or contribute to infection-related immune modulation. For example, CLEC10A’s engagement with certain viral glycans may help in trapping and processing viral particles by dendritic cells or macrophages, enhancing immune responses against viruses.

Autoimmune Disorders:

• CLEC10A’s role in recognizing self-glycoproteins suggests it may influence autoimmune responses. In autoimmune diseases where abnormal glycosylation patterns are present, such as rheumatoid arthritis or systemic lupus erythematosus, CLEC10A may interact abnormally with self-antigens, potentially exacerbating inflammation or modulating immune cell activity in affected tissues.

Cancer:

• CLEC10A’s recognition of aberrant glycosylation on cancer cells makes it relevant in cancer immunology. Tumor-associated carbohydrate antigens (TACAs) are common on cancer cells and can be recognized by CLEC10A. Research is ongoing to determine if CLEC10A’s interactions with TACAs can be harnessed for cancer immunotherapy or to enhance immune surveillance of tumors. Additionally, some cancers may exploit CLEC10A to avoid immune detection by altering their glycosylation profiles, impacting immune cell recruitment and activation.

Allergic Inflammation:

• CLEC10A’s involvement in modulating immune cell activity may also contribute to allergic inflammation. It has been found on cells in allergic environments, where its engagement with allergens could influence macrophage or dendritic cell responses, potentially exacerbating or ameliorating allergic reactions.

Summary

CLEC10A (CD301/MGL) is a C-type lectin receptor primarily expressed on macrophages and dendritic cells, where it recognizes terminal galactose and GalNAc residues on glycosylated antigens. Its structure, with a well-defined C-type lectin domain, transmembrane domain, and cytoplasmic tail, supports its function in pathogen recognition, immune regulation, and potentially in immune tolerance. CLEC10A’s unique carbohydrate specificity situates it as a crucial receptor in pathogen capture, immune modulation, and even immune surveillance in cancer, given its capacity to bind to tumor-associated glycan structures.

Clinically, CLEC10A is implicated in various conditions, including infectious diseases, autoimmune disorders, and cancer, largely due to its ability to recognize both self and foreign glycosylated antigens. By participating in immune surveillance, CLEC10A modulates innate immune responses and serves as a bridge to adaptive immunity, particularly through endocytosis and antigen processing. Its role in recognizing abnormal glycosylation patterns makes it a potential target for therapeutic approaches in infectious disease, cancer, and autoimmune conditions. As research advances, CLEC10A remains a key focus in understanding glycan-dependent immune processes and their applications in immunology and therapeutic development.