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Published on: May 19, 2020
Forming a complex with MHC class I molecules interferes with mouse CD1d functional expression
Renukaradhya J Gourapura1, Masood A Khan, Richard M Gallo
1Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, Indiana, USA.
Insights
Major Histocompatibility Complex class I (MHC class I) molecules regulate CD1d function by physically associating with CD1d. This association masks CD1d, impacting lipid antigen presentation to Natural Killer T (NKT) cells.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- CD1d molecules are structurally similar to MHC class I but present lipid antigens.
- MHC class I molecules typically present peptide antigens.
Purpose of the Study:
- To investigate the physical association between MHC class I and CD1d molecules.
- To determine the functional consequences of this association on CD1d-mediated antigen presentation to NKT cells.
Main Methods:
- Acid stripping of MHC class I molecules from antigen-presenting cells.
- Analysis of surface expression of murine CD1d.
- Assessment of CD1d-mediated antigen presentation to NKT cells.
- Comparison of NKT cell populations and CD1d antigen presentation in TAP1-/- mice versus wild-type mice.
Main Results:
- MHC class I molecules physically associate with and regulate the surface expression of mouse CD1d.
- Low pH acid stripping of MHC class I increased surface CD1d expression and augmented CD1d-mediated antigen presentation to NKT cells.
- TAP1-/- mice exhibited a higher percentage of type I NKT cells and enhanced CD1d antigen presentation by dendritic cells.
Conclusions:
- MHC class I molecules regulate NKT cell function by masking CD1d.
- This interaction influences the availability of CD1d for lipid antigen presentation.
Abstract:
CD1d molecules are structurally similar to MHC class I, but present lipid antigens as opposed to peptides. Here, we show that MHC class I molecules physically associate with (and regulate the functional expression of) mouse CD1d on the surface of cells. Low pH (3.0) acid stripping of MHC class I molecules resulted in increased surface expression of murine CD1d on antigen presenting cells as well as augmented CD1d-mediated antigen presentation to NKT cells. Consistent with the above results, TAP1-/- mice were found to have a higher percentage of type I NKT cells as compared to wild type mice. Moreover, bone marrow-derived dendritic cells from TAP1-/- mice showed increased antigen presentation by CD1d compared to wild type mice. Together, these results suggest that MHC class I molecules can regulate NKT cell function, in part, by masking CD1d.
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