CD207 - CD207 molecule |Elisa - Clia - Antibody - Protein

Background

CD207, commonly referred to as langerin, is a C-type lectin receptor primarily expressed in Langerhans cells (LCs), a specialized subset of dendritic cells residing in the epidermis and other epithelial surfaces, such as the respiratory and digestive tracts. CD207 plays a critical role in immune surveillance by recognizing and binding to specific carbohydrate structures on pathogens, facilitating their capture and internalization. This receptor is crucial for pathogen recognition and uptake, which supports the initiation of adaptive immune responses. Encoded by the CD207 gene, CD207 is instrumental in the function and identity of Langerhans cells. It is also the defining marker for Langerhans cells, distinguishing them from other dendritic cell subsets.

Langerhans cells use CD207 to capture and internalize pathogens, leading to antigen processing and subsequent presentation to T cells, which is central to adaptive immunity. CD207’s unique feature is its ability to induce the formation of Birbeck granules—distinctive organelles with a rod and vesicle shape that are exclusive to Langerhans cells. These granules are believed to support the specialized antigen-processing function of CD207.

Protein Structure

The CD207 protein is a type II transmembrane protein with a distinct organization that supports its role in pathogen recognition, endocytosis, and antigen processing. CD207 has the following structural components:

1. Extracellular Domain: The extracellular region of CD207 is crucial for its role in binding to carbohydrates on pathogens. It is organized as follows:

• C-Type Lectin Domain (CTLD): CD207 contains a single C-type lectin-like domain within its extracellular region, which facilitates carbohydrate binding in a calcium-dependent manner. This domain specifically recognizes mannose-containing glycoconjugates found on the surfaces of certain pathogens, such as fungi, bacteria, and viruses. This mannose specificity is essential for targeting pathogens that possess distinct glycosylation patterns, differentiating them from host cells.
• Carbohydrate Recognition Domain (CRD): Embedded within the C-type lectin-like domain, the carbohydrate recognition domain (CRD) enables CD207 to recognize and bind specific sugar motifs. The CRD is particularly sensitive to mannose-rich glycans, which is a characteristic shared by many pathogen surfaces.

1. Transmembrane Domain: CD207 contains a single transmembrane segment that anchors it in the plasma membrane of Langerhans cells. As a type II transmembrane protein, the C-terminal portion of CD207 is located extracellularly, while the N-terminal resides within the cytoplasm. This orientation is essential for supporting endocytosis, as it positions the extracellular domain to capture pathogens in the cellular environment.
2. Cytoplasmic Tail: The short cytoplasmic tail of CD207 contains motifs that are necessary for internalization of bound ligands and signaling functions. This domain is associated with clathrin-mediated endocytosis, allowing CD207 to internalize bound pathogens into vesicles. The cytoplasmic tail also has a sorting signal, which directs the receptor-ligand complex into the Birbeck granules, facilitating intracellular antigen processing and subsequent presentation.

The structure of CD207, including its lectin-like domain and cytoplasmic sorting signals, is tailored for efficient pathogen recognition and uptake, positioning it as a crucial receptor in the immune functions of Langerhans cells.

Classification and Subtypes

CD207 is classified as part of the C-type lectin receptor (CLR) family, known for their ability to bind carbohydrates through C-type lectin-like domains in a calcium-dependent manner. Within this family, CD207 is categorized under the endocytic CLR subgroup, as it mediates pathogen capture and internalization. CD207 does not have subtypes but is uniquely expressed by Langerhans cells, which distinguishes it from other members of the CLR family expressed on dendritic cells or macrophages.

The absence of major subtypes or isoforms of CD207 reflects its specialized function and expression, which is largely restricted to Langerhans cells in the epidermis and other mucosal surfaces.

Function and Biological Significance

CD207 has several key functions essential to the role of Langerhans cells in immune defense:

1. Pathogen Recognition and Internalization: CD207 recognizes and binds to specific mannose-containing glycoconjugates on the surfaces of pathogens, including fungi, bacteria, and some viruses. Upon binding, CD207 internalizes these pathogens through endocytosis, facilitating their transport into endosomal compartments where they can be processed. This uptake allows Langerhans cells to capture antigens from the environment efficiently, which is the first step in antigen presentation and subsequent T cell activation.
2. Antigen Processing and Presentation: After capturing and internalizing pathogens, CD207 directs them to Birbeck granules for processing. The structure of Birbeck granules is thought to aid in the processing of these antigens into smaller peptides, which are then loaded onto MHC class II molecules for presentation to CD4+ T helper cells. This function is crucial for initiating adaptive immune responses and for training the immune system to recognize specific pathogens. Birbeck granules appear to be specialized organelles for antigen processing, making CD207 an essential component of antigen presentation in Langerhans cells.
3. Immune Surveillance and Immune Tolerance: By presenting antigens to T cells, CD207+ Langerhans cells play a role in immune surveillance, enabling the immune system to recognize and respond to a broad array of pathogens. In addition to pathogen detection, CD207 also contributes to immune tolerance, as Langerhans cells can present self-antigens or environmental antigens in a way that does not lead to an inflammatory response. This feature helps prevent overreactive immune responses and maintains tissue homeostasis in epithelial barriers.
4. Role in Viral Infection: CD207 is known to interact with certain viruses, such as HIV, where it binds and internalizes viral particles. Although this is part of the immune function of Langerhans cells, some viruses can exploit CD207 to gain entry into cells, evade immune responses, or spread within the host.

Clinical Issues

Given its role in immune defense, CD207 has been studied in the context of several clinical conditions, including infections, inflammatory diseases, and malignancies:

1. Infectious Diseases: CD207’s role in pathogen recognition makes it essential for defense against infections, especially fungal pathogens like Candida albicans and Mycobacterium leprae, the causative agent of leprosy. Some pathogens, however, can exploit CD207 to enter Langerhans cells without triggering immune responses, thus facilitating infection persistence. For instance, HIV binds to CD207 on Langerhans cells, which may contribute to viral entry and persistence in the mucosal tissues. Modulating CD207's interaction with these pathogens could offer therapeutic options to prevent or limit such infections.
2. Inflammatory Skin Disorders: CD207 has been implicated in various inflammatory skin diseases, where Langerhans cells play a prominent role in modulating immune responses. In conditions like atopic dermatitis and psoriasis, altered CD207 function or abnormal Langerhans cell activity contributes to local inflammation and immune dysregulation. Targeting CD207 activity on Langerhans cells may help to develop new treatments to manage chronic skin inflammation and autoimmune skin disorders.
3. Langerhans Cell Histiocytosis (LCH): This rare disease is characterized by the abnormal proliferation of Langerhans cells, often expressing high levels of CD207. LCH can affect various organs, including bone, skin, and the central nervous system, and is associated with the accumulation of CD207+ cells in these tissues. While the exact cause of LCH is not fully understood, it is believed to involve mutations leading to uncontrolled Langerhans cell proliferation. Monitoring CD207 expression and targeting CD207+ cells are considered in the diagnostic and therapeutic approaches to managing LCH.
4. Cancer Immunotherapy: Given its role in antigen presentation, CD207 has been explored as a target for immunotherapy in cancer. By targeting tumor-associated antigens to CD207+ Langerhans cells, it may be possible to stimulate anti-tumor immunity. Approaches that leverage CD207’s antigen-capturing capabilities could potentially enhance the immune system's ability to recognize and destroy cancer cells, particularly in skin and mucosal cancers.

Summary

CD207, or langerin, is a C-type lectin receptor specific to Langerhans cells in the epidermis and certain mucosal tissues. As a type II transmembrane protein, CD207 possesses a unique structure featuring a C-type lectin-like domain that facilitates carbohydrate binding, a transmembrane region anchoring it to the membrane, and a cytoplasmic tail involved in endocytosis. This structure allows CD207 to function as a pathogen recognition receptor, capturing mannose-containing glycoconjugates on pathogens, internalizing them, and processing them in specialized organelles called Birbeck granules.

CD207 serves multiple functions, including pathogen recognition, immune surveillance, antigen processing, and presentation, making it a crucial receptor in the innate and adaptive immune responses. Clinically, CD207 is relevant in infections, inflammatory skin disorders, and in the rare disease Langerhans cell histiocytosis (LCH), where aberrant Langerhans cell proliferation is associated with disease pathology. Additionally, CD207’s antigen-presenting capacity has made it a potential target in cancer immunotherapy, where leveraging its properties could enhance anti-tumor immune responses.

In summary, CD207 plays a vital role in immune defense by enabling Langerhans cells to recognize and process pathogens. Its involvement in several clinical conditions highlights its importance in both normal immune function and disease, marking it as a significant target for therapeutic development in infection, inflammation, and oncology.