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Publication : Toll-dependent selection of microbial antigens for presentation by dendritic cells.

First Author  Blander JM Year  2006
Journal  Nature Volume  440
Issue  7085 Pages  808-12
PubMed ID  16489357 Mgi Jnum  J:107631
Mgi Id  MGI:3621580 Doi  10.1038/nature04596
Citation  Blander JM, et al. (2006) Toll-dependent selection of microbial antigens for presentation by dendritic cells. Nature 440(7085):808-12
abstractText  Dendritic cells constitutively sample the tissue microenvironment and phagocytose both microbial and host apoptotic cells. This leads to the induction of immunity against invading pathogens or tolerance to peripheral self antigens, respectively. The outcome of antigen presentation by dendritic cells depends on their activation status, such that Toll-like receptor (TLR)-induced dendritic cell activation makes them immunogenic, whereas steady-state presentation of self antigens leads to tolerance. TLR-inducible expression of co-stimulatory signals is one of the mechanisms of self/non-self discrimination. However, it is unclear whether or how the inducible expression of co-stimulatory signals would distinguish between self antigens and microbial antigens when both are encountered by dendritic cells during infection. Here we describe a new mechanism of antigen selection in dendritic cells for presentation by major histocompatibility complex class II molecules (MHC II) that is based on the origin of the antigen. We show that the efficiency of presenting antigens from phagocytosed cargo is dependent on the presence of TLR ligands within the cargo. Furthermore, we show that the generation of peptide-MHC class II complexes is controlled by TLRs in a strictly phagosome-autonomous manner.
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