Toll-dependent selection of microbial antigens for presentation by dendritic cells.
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.
Section of Immunobiology, Howard Hughes Medical Institute, Yale University School of Medicine, 300 Cedar Street, New Haven, Connecticut 06520, USA.
J Magarian
JM
Blander
Ruslan
R
Medzhitov
D000818:Animals; D017951:Antigen Presentation; D000946:Antigens, Fungal / Q000276:immunology* / Q000378:metabolism; D017209:Apoptosis; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D008024:Ligands; D008213:Lymphocyte Activation; D051379:Mice; D008815:Mice, Inbred Strains; D010587:Phagocytosis; D012441:Saccharomyces cerevisiae / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D051193:Toll-Like Receptors / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000946:Antigens, Fungal; D000949:Histocompatibility Antigens Class II; D007376:Interleukin-2; D008024:Ligands; D051193:Toll-Like Receptors