Abstract
Dendritic cells (DCs) are the most powerful antigen presenting cells (APCs) in the immune system. Therefore, they are able to take up antigen by phagocytosis, macropinocytosis or endocytosis, process it in the cytosol and present it to naive T cells. It is known that presentation of the immunodominant influenza virus nucleoprotein-derived CTL epitope is delayed in bone marrow-derived DCs (BMDCs) compared to non-professional APCs. This delay coincided with the formation of transient aggregations of ubiquitinated proteins (DALIS, dendritic cell aggresome-like induced structures), which contain probably defective ribosomal products (DRiPs). DRiPs appear in the cytosol of maturing DCs and macrophages. Normally, DRiPs are degraded rapidly by proteasomes. However, their storage in DALIS delays their degradation. So, it is hypothesized that DALIS can function as antigen depots allowing DCs to coordinate maturation and antigen presentation during their migration to the lymph nodes. Upon inhibition of several pathways among the in signal transduction pathways of DCs, like the phosphatidylinositol 3-kinase (PI3-K) or the mammalian target of Rapamycin (mTOR), the cells show a rendered maturation profile. The formation of DALIS is inhibited in these cells which can be expected to influence antigen processing and presentation.
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Abbreviations
- BMDC:
-
Bone marrow-derived dendritic cell
- CTL:
-
Cytotoxic T lymphocytes
- DALIS:
-
Dendritic cell aggresome-like induced structures
- DRiPs:
-
Defective ribosomal products
- mCMV:
-
Murine cytomegalovirus
- NP:
-
Nucleoprotein
- PI3-K:
-
Phosphatidylinositol 3-kinase
- mTOR:
-
Mammalian target of Rapamycin
- TLR:
-
Toll-like receptor
- LPS:
-
Lipopolysaccharid
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This work was supported by grants from the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 490, individual projects E6 to H.S. and E3 to R.H.).
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Faßbender, M., Herter, S., Holtappels, R. et al. Correlation of dendritic cell maturation and the formation of aggregates of poly-ubiquitinated proteins in the cytosol. Med Microbiol Immunol 197, 185–189 (2008). https://doi.org/10.1007/s00430-008-0091-4
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DOI: https://doi.org/10.1007/s00430-008-0091-4