CD1B - CD1b molecule |Elisa - Clia - Antibody - Protein

Background

CD1B is a transmembrane glycoprotein that belongs to the CD1 family, which is structurally related to major histocompatibility complex (MHC) class I molecules. Encoded by the CD1B gene, it is primarily involved in the presentation of lipid and glycolipid antigens to T-cells, particularly a subset of T-cells known as invariant natural killer T-cells (iNKT). CD1B molecules are critical for immune responses to mycobacterial and other pathogen-derived lipids. Unlike MHC molecules, CD1B specializes in presenting lipid-based antigens rather than peptide antigens. It is expressed on antigen-presenting cells (APCs) such as dendritic cells, monocytes, and certain thymocytes.

Protein Structure

CD1B is a 38 kDa glycoprotein that comprises three extracellular domains (α1, α2, and α3), a transmembrane domain, and a cytoplasmic tail:

1. Extracellular Domain: The α1 and α2 domains form the antigen-binding groove, which accommodates lipid and glycolipid antigens. This groove is hydrophobic, enabling efficient interaction with lipid tails of antigens.
2. α3 Domain: Structurally similar to β2-microglobulin-associated domains in MHC class I molecules, this domain interacts with the β2-microglobulin non-covalently, stabilizing the protein.
3. Antigen Binding: CD1B’s binding groove is more hydrophobic and deeper than other CD1 family members, allowing it to bind larger lipid antigens, such as mycolic acids from mycobacteria.
4. Membrane Localization: CD1B traffics through intracellular compartments, including the endosomal/lysosomal system, to load antigens, facilitated by its cytoplasmic tail that interacts with intracellular sorting machinery.

Classification and Subtypes

The CD1 family includes five isoforms in humans: CD1A, CD1B, CD1C, CD1D, and CD1E. These are classified based on their antigen-binding preferences and intracellular trafficking pathways:

• CD1B is unique in its ability to bind lipid antigens requiring acidic endosomal environments for optimal loading.
• CD1B shows specificity for bacterial lipids, including mycolic acids, lipoarabinomannan, and sulfatides.

Function and Biological Significance

The primary role of CD1B is antigen presentation to T-cells, specifically CD1-restricted T-cells:

1. Antigen Presentation: CD1B captures lipid antigens in endosomal compartments, loading them into its hydrophobic groove and presenting them on the surface of APCs to activate T-cells.
2. Immune Response to Lipid Antigens: CD1B plays a pivotal role in the recognition of mycobacterial lipids, crucial in the immune response against tuberculosis (TB) and leprosy.
3. Endosomal Localization: CD1B traffics through endosomes and lysosomes, which provide an acidic environment for antigen loading. This trafficking relies on the cytoplasmic tail of CD1B, containing sorting signals that mediate interactions with adapter proteins.
4. iNKT Cell Activation: CD1B-restricted presentation activates iNKT cells, which release cytokines such as IFN-γ and IL-4, bridging innate and adaptive immunity.

CD1B also plays roles in maintaining immune tolerance by presenting self-lipids, preventing autoreactivity. Its role in detecting microbial lipids highlights its importance in defending against intracellular pathogens like Mycobacterium tuberculosis.

Clinical Issues

1. Tuberculosis and Leprosy: CD1B plays a central role in recognizing mycobacterial lipids, making it crucial for immunity against Mycobacterium tuberculosis and Mycobacterium leprae. Impairments in CD1B expression or function can increase susceptibility to these infections.
2. Autoimmunity: Dysregulation in CD1B-mediated self-lipid presentation may contribute to autoimmune diseases, where self-reactive T-cells are inappropriately activated.
3. Cancer: Altered CD1B expression has been noted in some cancers, where immune evasion may involve downregulation of CD1 molecules, including CD1B.
4. Genetic Mutations: Mutations affecting CD1B’s antigen-loading pathways may impair its ability to present microbial lipids, reducing immune efficiency.

Summary

CD1B is a specialized antigen-presenting molecule that bridges innate and adaptive immunity by presenting lipid antigens to T-cells. Its hydrophobic antigen-binding groove, β2-microglobulin stabilization, and trafficking to acidic compartments enable it to recognize complex lipid molecules, particularly those from mycobacterial pathogens. CD1B is essential for immunity against intracellular bacteria like Mycobacterium tuberculosis, and its dysregulation has implications for infections, autoimmunity, and cancer. This molecule remains a critical focus for understanding immune defense mechanisms and designing therapies for infectious and autoimmune diseases.