CD1C - CD1c molecule |Elisa - Clia - Antibody - Protein

Background

The CD1C molecule is a member of the CD1 family of glycoproteins, which play a critical role in the immune system by presenting lipid and glycolipid antigens to T cells. Unlike major histocompatibility complex (MHC) class I and II molecules, which primarily present peptide antigens, CD1 molecules specialize in the presentation of lipids, making them essential players in immune responses against lipid-containing pathogens like mycobacteria. CD1C, in particular, is one of the most studied isoforms in the CD1 family due to its role in presenting antigens to T cells, especially CD1c-restricted T cells, which are important in the defense against bacterial infections, especially those involving mycobacteria.

CD1C is expressed predominantly on antigen-presenting cells (APCs), such as dendritic cells, B cells, and macrophages, which are crucial for initiating adaptive immune responses. The molecule plays a significant role in shaping the immune response to lipid antigens, facilitating the recognition and elimination of microbial invaders, especially those with complex lipid envelopes, such as Mycobacterium tuberculosis. CD1C is also implicated in modulating immune responses in autoimmune diseases, cancers, and other conditions where the immune system’s ability to recognize and respond to lipid antigens is altered.

Protein Structure

The CD1C protein is a transmembrane glycoprotein that shares structural similarities with both MHC class I and II molecules. It consists of a heavy chain (~48 kDa), which is non-covalently associated with β2-microglobulin (~12 kDa), a small protein essential for the stability and function of CD1C. The heavy chain of CD1C contains three extracellular domains (α1, α2, and α3), a transmembrane domain, and a short cytoplasmic tail.

Primary Structure:

• α1 and α2 domains: These domains form a groove or cleft that binds lipid antigens. The hydrophobic environment of the groove is specifically adapted to accommodate the hydrophobic tails of lipid molecules, unlike the peptide-binding grooves of MHC molecules.
• α3 domain: This domain is similar to the α3 domain of MHC class I molecules, and it interacts with β2-microglobulin to stabilize the structure of the complex.
• Transmembrane and cytoplasmic domains: The transmembrane region anchors the molecule into the cell membrane, while the short cytoplasmic tail is involved in intracellular trafficking and localization of the molecule to endosomes, where it can acquire lipid antigens.

The lipid-binding groove of CD1C is deeper and more flexible compared to other CD1 isoforms, allowing it to accommodate a broader range of lipid antigens, including diacylglycerols and phospholipids. This broader specificity enhances its ability to present diverse lipid antigens to T cells. The CD1C molecule can bind lipids through hydrophobic interactions between the lipid’s alkyl chains and the hydrophobic groove of CD1C, while the polar head groups of lipids often interact with the surrounding hydrophilic regions of the binding pocket.

Secondary and Tertiary Structure:

The overall secondary structure of CD1C is a combination of α-helices and β-sheets, with the β-sheets forming the base of the antigen-binding groove and the α-helices flanking either side of the groove. This conformation creates a unique lipid-binding cleft, which is designed to present lipid antigens on the cell surface in a manner that is recognized by T cell receptors (TCRs) of CD1c-restricted T cells.

The tertiary structure of CD1C, similar to other CD1 molecules, allows it to sample lipid antigens from the extracellular environment or from within intracellular compartments such as the endosomes. CD1C is trafficked between the cell surface and endosomal compartments, where it encounters exogenous lipids (such as those derived from pathogens) and endogenous lipids (derived from self) that it can present to T cells.

Classification and Subtypes

CD1C is one of the five CD1 isoforms (CD1A, CD1B, CD1C, CD1D, and CD1E) classified based on their structure and the type of antigens they present. These molecules are divided into group 1 (CD1A, CD1B, CD1C, and CD1E) and group 2 (CD1D). CD1C is part of group 1 CD1 molecules, which are predominantly involved in presenting exogenous lipid antigens to T cells, particularly non-peptide antigens from microbes.

Unlike CD1D, which presents lipids to natural killer T (NKT) cells, CD1C presents antigens to CD1c-restricted T cells, a subset of αβ T cells that recognize lipid antigens.

Function and Biological Significance

Antigen Presentation:

The primary function of CD1C is the presentation of lipid antigens to CD1c-restricted T cells, facilitating the recognition of microbial lipids and glycolipids. CD1C is capable of presenting a wide range of lipid antigens, including glycolipids, sphingolipids, and phospholipids, derived from both microbial pathogens and endogenous cellular sources.

• Microbial Lipid Antigens: CD1C plays a critical role in the immune response to lipid-containing pathogens, particularly Mycobacterium tuberculosis and other mycobacteria. The recognition of mycobacterial glycolipids, such as phosphatidylinositol mannosides (PIMs), by CD1c-restricted T cells is crucial for initiating protective immune responses against these intracellular pathogens.
• Endogenous Lipids: CD1C can also present self-lipids, which may have implications in immune regulation and the maintenance of self-tolerance. However, dysregulation of this process may contribute to autoimmune diseases.

Immune Response Modulation:

CD1C plays a dual role in immunity by both initiating protective responses against pathogens and regulating immune homeostasis. The presentation of microbial lipids by CD1C to T cells results in the activation of pro-inflammatory responses, which are critical for controlling infections. In contrast, the presentation of self-lipids may have regulatory functions, potentially contributing to immune tolerance mechanisms.

Cross-Talk with Dendritic Cells:

CD1C is highly expressed on dendritic cells (DCs), which are professional antigen-presenting cells responsible for capturing antigens, processing them, and presenting them to T cells. The expression of CD1C on DCs enhances their ability to present lipid antigens to T cells, promoting the initiation of adaptive immune responses.

Clinical Issues

Infectious Diseases:

CD1C is critically involved in the immune response to intracellular pathogens, particularly mycobacteria. Defects in CD1C expression or function could lead to impaired immune responses to mycobacterial infections, such as tuberculosis. Polymorphisms in the CD1C gene have been investigated in the context of susceptibility to infectious diseases, with some studies suggesting that genetic variations in CD1C may influence the outcome of infections.

Autoimmune Diseases:

Aberrant presentation of self-lipids by CD1C has been implicated in the pathogenesis of autoimmune diseases. For example, altered lipid antigen presentation could lead to the activation of autoreactive T cells, contributing to the breakdown of self-tolerance and the development of autoimmune conditions such as multiple sclerosis and type 1 diabetes. Research into the role of CD1C in autoimmunity is ongoing, with the aim of understanding how dysregulated lipid antigen presentation may drive disease processes.

Cancer:

The role of CD1C in cancer immunity is less well-understood, but it is known that CD1C can present lipid antigens derived from tumor cells to T cells. This suggests that CD1C may play a role in tumor immunosurveillance, where the immune system recognizes and eliminates cancerous cells. However, tumors may also exploit CD1C pathways to evade immune detection by altering lipid antigen presentation.

Therapeutic Potential:

Targeting CD1C for therapeutic purposes is an area of active research. Potential strategies include:

• Vaccine Development: Leveraging CD1C’s ability to present microbial lipid antigens to develop vaccines, particularly for pathogens like Mycobacterium tuberculosis.
• Immunotherapy: Modulating CD1C activity in cancer or autoimmune diseases to enhance immune responses or restore tolerance.

Summary

The CD1C molecule is a member of the CD1 family of glycoproteins that present lipid and glycolipid antigens to T cells. It plays a crucial role in the immune response against lipid-containing pathogens, particularly mycobacteria, by presenting lipid antigens to CD1c-restricted T cells. Structurally, CD1C is similar to MHC class I molecules but has a specialized lipid-binding groove that accommodates a broad range of lipid antigens. CD1C is primarily expressed on antigen-presenting cells, such as dendritic cells and macrophages, where it modulates immune responses.

CD1C is implicated in both protective immune responses against pathogens and in the regulation of immune tolerance. Dysregulation of CD1C function may contribute to infectious diseases, autoimmune disorders, and potentially cancer. Given its pivotal role in lipid antigen presentation, CD1C is an attractive target for therapeutic interventions in infectious diseases, autoimmune disorders, and cancer immunotherapy. Further research into CD1C’s role in health and disease will help in the development of novel immunotherapeutic strategies that exploit its unique capacity to present lipid antigens