Back to Search
Start Over
Internalization and endosomal degradation of receptor-bound antigens regulate the efficiency of cross presentation by human dendritic cells.
- Source :
-
Blood [Blood] 2012 Sep 06; Vol. 120 (10), pp. 2011-20. Date of Electronic Publication: 2012 Jul 12. - Publication Year :
- 2012
-
Abstract
- Dendritic cells (DCs) can capture extracellular antigens and load resultant peptides on to MHC class I molecules, a process termed cross presentation. The mechanisms of cross presentation remain incompletely understood, particularly in primary human DCs. One unknown is the extent to which antigen delivery to distinct endocytic compartments determines cross presentation efficiency, possibly by influencing antigen egress to the cytosol. We addressed the problem directly and quantitatively by comparing the cross presentation of identical antigens conjugated with antibodies against different DC receptors that are targeted to early or late endosomes at distinct efficiencies. In human BDCA1+ and monocyte-derived DCs, CD40 and mannose receptor targeted antibody conjugates to early endosomes, whereas DEC205 targeted antigen primarily to late compartments. Surprisingly, the receptor least efficient at internalization, CD40, was the most efficient at cross presentation. This did not reflect DC activation by CD40, but rather its relatively poor uptake or intra-endosomal degradation compared with mannose receptor or DEC205. Thus, although both early and late endosomes appear to support cross presentation in human DCs, internalization efficiency, especially to late compartments, may be a negative predictor of activity when selecting receptors for vaccine development.
- Subjects :
- Amino Acid Sequence
Antigen-Antibody Complex metabolism
Antigens, CD immunology
Antigens, CD metabolism
Dendritic Cells cytology
Dendritic Cells metabolism
Endosomes metabolism
Histocompatibility Antigens Class I immunology
Histocompatibility Antigens Class I metabolism
Humans
Immunity, Innate
Lectins, C-Type immunology
Lectins, C-Type metabolism
Mannose Receptor
Mannose-Binding Lectins immunology
Mannose-Binding Lectins metabolism
Membrane Glycoproteins immunology
Membrane Glycoproteins metabolism
Minor Histocompatibility Antigens
Molecular Sequence Data
Peptides immunology
Peptides metabolism
Primary Cell Culture
Receptors, Cell Surface immunology
Receptors, Cell Surface metabolism
Receptors, Immunologic immunology
Receptors, Immunologic metabolism
Antigen-Antibody Complex immunology
Cross-Priming
Dendritic Cells immunology
Endocytosis immunology
Endosomes immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1528-0020
- Volume :
- 120
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 22791285
- Full Text :
- https://doi.org/10.1182/blood-2012-01-402370