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Published on: April 18, 2016
Low expression level but potent antigen presenting function of CD1d on monocyte lineage cells
F M Spada1, F Borriello, M Sugita
1Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Insights
Monocyte lineage cells are potent stimulators of CD1d-restricted immune responses, despite low surface expression. Their endocytic system is crucial for efficient antigen loading onto CD1d, highlighting unique CD1d regulation.
Area of Science:
- Immunology
- Cell Biology
Background:
- CD1d is a crucial antigen-presenting molecule for Natural Killer T (NK T) cell selection and activation.
- NK T cells are a conserved T cell subset integral to immune responses.
Purpose of the Study:
- To investigate the expression, regulation, and function of human CD1d in myeloid-derived antigen-presenting cells (APCs).
- To understand the role of monocyte lineage cells in CD1d-restricted immune responses.
Main Methods:
- Analysis of CD1d expression and regulation in monocytes, monocyte-derived dendritic cells, and macrophages.
- Functional assays using NK T cell clones and the synthetic glycolipid antigen alpha-galactosyl ceramide.
- Microscopic localization studies of CD1d within monocyte lineage cells.
Main Results:
- CD1d is expressed as a mature glycoprotein by myeloid APCs, with constitutive expression not significantly upregulated by common cytokines.
- Despite low surface levels, myeloid cells are highly effective APCs for NK T cell responses to alpha-galactosyl ceramide.
- CD1d predominantly localizes to the endocytic system in monocyte lineage cells, facilitating efficient antigen loading.
Conclusions:
- Monocyte lineage cells are significant stimulators of CD1d-restricted immune responses.
- The unique regulation and endocytic localization of CD1d in these cells are critical for potent antigen presentation.
Abstract:
CD1d is a key antigen-presenting molecule involved in the selection and activation of a highly conserved T cell subset known as NK T cells. In this study, we analyzed the expression, regulation and function of human CD1d by various antigen-presenting cells (APC) of myeloid origin, including circulating monocytes, monocyte-derived dendritic cells and macrophages. CD1d was expressed as a mature glycoprotein by these cells, and unlike the other members of the human CD1 family its expression was constitutive and was not strongly up-regulated by GM-CSF and IL-4 or a range of other cytokines. Despite their remarkably low surface expression of CD1d, all myeloid lineage cells tested were extremely potent APC for responses of NK T cell clones to the synthetic glycolipid antigen, alpha-galactosyl ceramide. Prominent localization of CD1d to the endocytic system of monocyte lineage cells was observed, and functional studies suggested that this was important for achieving efficient antigen loading onto CD1d. Overall, these results support the view that monocyte lineage cells are important stimulators of CD1d-restricted immune responses, while also underscoring the unique regulation of CD1d expression by these cells.
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