Related Experiment Video
Updated: Aug 8, 2026
Integrate Imaging Flow Cytometry and Transcriptomic Profiling to Evaluate Altered Endocytic CD1d Trafficking
Published on: October 29, 2018
CD1c molecules broadly survey the endocytic system
M Sugita1, N van Der Wel, R A Rogers
1Lymphocyte Biology Section, Division of Rheumatology, Immunology and Allergy, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Insights
CD1c molecules uniquely survey the entire endocytic system for lipid antigens, unlike other antigen-presenting molecules. This broad sampling and independence from acidic environments enhance microbe detection by antigen-presenting cells.
Area of Science:
- Immunology
- Cell Biology
Background:
- Antigen-presenting cells (APCs) detect microbes by sampling intracellular compartments.
- Major histocompatibility complex (MHC) class I and II present peptide antigens from cytosol and late endosomes.
- CD1a and CD1b present lipid antigens from early recycling endosomes and late endocytic compartments, respectively.
Purpose of the Study:
- To investigate the intracellular distribution and antigen-presentation capabilities of CD1c.
- To compare CD1c's sampling and functional requirements with other CD1 isoforms and MHC molecules.
Main Methods:
- Immunofluorescence microscopy to determine CD1c localization within the endocytic system.
- Functional assays assessing antigen presentation by CD1c under varying pH conditions.
Main Results:
- CD1c distributes broadly across the endocytic system, including recycling endosomes and late endocytic compartments.
- Unlike CD1b, CD1c-mediated antigen presentation is not dependent on acidic vesicular environments.
- CD1c is expressed on APCs like Langerhans cells and B cells, sometimes in the absence of other CD1s.
Conclusions:
- CD1c exhibits a unique, comprehensive sampling of the endocytic system for lipid antigens.
- CD1c's functional independence from acidity broadens its role in lipid antigen surveillance.
- CD1c plays a vital role in detecting diverse lipid antigens, particularly when other CD1 molecules are absent.
Abstract:
The ability of antigen-presenting cells to sample distinct intracellular compartments is crucial for microbe detection. Major histocompatibility complex class I and class II molecules sample the cytosol or the late endocytic compartment, allowing detection of microbial peptide antigens that arise in distinct intracellular compartments. In contrast, CD1a and CD1b molecules mediate the presentation of lipid and glycolipid antigens and differentially sample early recycling endosomes or late endocytic compartments, respectively, that contain distinct sets of lipid antigens. Here, we show that, unlike the other CD1 isoforms or major histocompatibility complex molecules that each sample restricted only intracellular compartments, CD1c is remarkable in that it distributes broadly throughout the endocytic system and is expressed in both recycling endosomes and late endocytic compartments. Further, in contrast to CD1b, which requires an acidic environment to function, antigen presentation by CD1c was able to overcome dependence on vesicular acidification. Because CD1c is expressed on essential antigen-presenting cells, such as epidermal Langerhans cells (in the absence of CD1b), or on B cells (without CD1a or -b), we suggest that CD1c molecules allow a comprehensive survey for lipid antigens throughout the endocytic system even in the absence of other CD1 isoforms.
Related Concept Videos
01:38Receptor-mediated Endocytosis
01:20Receptor-mediated Endocytosis
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
01:28The Early Endosome: Endocytosis of Transferrin
00:58Recycling Endosomes and Transcytosis
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
01:36Delivery Pathways to the Lysosome
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
01:20Receptor-Mediated Endocytosis
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...