Abstract:
:Recognition of self-antigen-derived epitopes presented by major histocompatibility complex class II (MHC II) molecules on thymic epithelial cells (TECs) is critical for the generation of a functional and self-tolerant CD4 T-cell repertoire. Whereas haematopoietic antigen-presenting cells generate MHC-II-peptide complexes predominantly through the processing of endocytosed polypeptides, it remains unknown if and how TECs use unconventional pathways of antigen presentation. Here we address the role of macroautophagy, a process that has recently been shown to allow for endogenous MHC II loading, in T-cell repertoire selection in the mouse thymus. In contrast to most other tissues, TECs had a high constitutive level of autophagy. Genetic interference with autophagy specifically in TECs led to altered selection of certain MHC-II-restricted T-cell specificities and resulted in severe colitis and multi-organ inflammation. Our findings indicate that autophagy focuses the MHC-II-peptide repertoire of TECs on their intracellular milieu, which notably comprises a wide array of otherwise strictly 'tissue-specific' self antigens. In doing so, it contributes to T-cell selection and is essential for the generation of a self-tolerant T-cell repertoire.
journal_name
Naturejournal_title
Natureauthors
Nedjic J,Aichinger M,Emmerich J,Mizushima N,Klein Ldoi
10.1038/nature07208subject
Has Abstractpub_date
2008-09-18 00:00:00pages
396-400issue
7211eissn
0028-0836issn
1476-4687pii
nature07208journal_volume
455pub_type
杂志文章相关文献
NATURE文献大全abstract::Relative motion is one of the most salient cues for segmentation of a visual scene into separate objects. This is illustrated by the vivid contours that are perceived when random dot patterns move in different directions. Once motion is halted in such displays the segmentation contours disappear. This makes random dot...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/363541a0
更新日期:1993-06-10 00:00:00
abstract::Bilingual individuals need effective mechanisms to prevent interference from one language while processing material in the other. Here we show, using event-related brain potentials and functional magnetic resonance imaging (fMRI), that words from the non-target language are rejected at an early stage before semantic a...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/4151026a
更新日期:2002-02-28 00:00:00
abstract::Cell line misidentification, contamination and poor annotation affect scientific reproducibility. Here we outline simple measures to detect or avoid cross-contamination, present a framework for cell line annotation linked to short tandem repeat and single nucleotide polymorphism profiles, and provide a catalogue of sy...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature14397
更新日期:2015-04-16 00:00:00
abstract::Cosmological models in which dark matter consists of cold elementary particles predict that the dark halo population should extend to masses many orders of magnitude below those at which galaxies can form1-3. Here we report a cosmological simulation of the formation of present-day haloes over the full range of observe...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/s41586-020-2642-9
更新日期:2020-09-01 00:00:00
abstract::The discovery of a plume of water vapour and ice particles emerging from warm fractures ('tiger stripes') in Saturn's small, icy moon Enceladus raised the question of whether the plume emerges from a subsurface liquid source or from the decomposition of ice. Previous compositional analyses of particles injected by the...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature10175
更新日期:2011-06-22 00:00:00
abstract::Eukaryotic cells seem to use GTP hydrolysis to regulate vesicular traffic in exocytosis and endocytosis. The best evidence for this comes from studies on the yeast Saccharomyces cerevisiae that have identified two small Ras-related GTP-binding proteins, Sec4p and Ypt1p, which control distinct stages of the secretory p...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/345553a0
更新日期:1990-06-07 00:00:00
abstract:: ...
journal_title:Nature
pub_type: 信件
doi:10.1038/d41586-019-00549-4
更新日期:2019-02-01 00:00:00
abstract::The detection of electron spins associated with single defects in solids is a critical operation for a range of quantum information and measurement applications under development. So far, it has been accomplished for only two defect centres in crystalline solids: phosphorus dopants in silicon, for which electrical rea...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12081
更新日期:2013-05-02 00:00:00
abstract::It is currently debated whether segmentation in different animal phyla has a common origin and shares a common genetic mechanism. The apparent use of different genetic networks in arthropods and vertebrates has become a strong argument against a common origin of segmentation. Our knowledge of arthropod segmentation is...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01682
更新日期:2003-06-19 00:00:00
abstract::The extent to which an organism is selected to invest in defences against pathogens and parasites depends on the advantages that ensue should infection occur, but also on the costs of maintaining defences in the absence of infection. The presence of heritable variation in resistance suggests that costs exist, but we k...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/38483
更新日期:1997-09-18 00:00:00
abstract::An amendment to this paper has been published and can be accessed via a link at the top of the paper. ...
journal_title:Nature
pub_type: 已发布勘误
doi:10.1038/s41586-020-2544-x
更新日期:2020-08-01 00:00:00
abstract::Demethylation at distinct lysine residues in histone H3 by lysine-specific demethylase 1 (LSD1) causes either gene repression or activation. As a component of co-repressor complexes, LSD1 contributes to target gene repression by removing mono- and dimethyl marks from lysine 4 of histone H3 (H3K4). In contrast, during ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature08839
更新日期:2010-04-01 00:00:00
abstract::The Milankovitch theory states that global climate variability on orbital timescales from tens to hundreds of thousands of years is dominated by the summer insolation at high northern latitudes. The supporting evidence includes reconstructed air temperatures in Antarctica that are nearly in phase with boreal summer in...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature09825
更新日期:2011-03-03 00:00:00
abstract::Exchange dynamics between molecules free in solution and bound to the surface of a large supramolecular structure, a polymer, a membrane or solid support are important in many phenomena in biology and materials science. Here we present a novel and generally applicable solution NMR technique, known as dark-state exchan...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature10577
更新日期:2011-10-30 00:00:00
abstract::An increase in free calcium triggers catecholamine secretion from chromaffin cells and calmodulin is strongly implicated as the intracellular Ca2+ receptor. In our recent studies of calmodulin action in the chromaffin cell, micromolar Ca2+ concentrations resulted in calmodulin and cytosolic proteins becoming bound to ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/301432a0
更新日期:1983-02-03 00:00:00
abstract::During formation of the neuromuscular junction, acetylcholine receptors in the endplate membrane become metabolically stabilized under neural control, their half-life increasing from about 1 day to about 10 days. The metabolic stability of the receptors is regulated by the electrical activity induced in the muscle by ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/349337a0
更新日期:1991-01-24 00:00:00
abstract::Chick embryo fibroblasts (CEF) infected with avian sarcoma virus become rapidly transformed as a result of expression of the viral src gene in the form of a single polypeptide of molecular weight 60,000 (pp60src) with protein kinase activity and suggested preferential association with the plasma membrane. Studies with...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/287241a0
更新日期:1980-09-18 00:00:00
abstract::Comparative mapping, which compares the location of homologous genes in different species, is a powerful tool for studying genome evolution. Comparative maps suggest that rates of chromosomal change in mammals can vary from one to ten rearrangements per million years. On the basis of these rates we would expect 84 to ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/46555
更新日期:1999-11-25 00:00:00
abstract::The ability to abstract principles or rules from direct experience allows behaviour to extend beyond specific circumstances to general situations. For example, we learn the 'rules' for restaurant dining from specific experiences and can then apply them in new restaurants. The use of such rules is thought to depend on ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35082081
更新日期:2001-06-21 00:00:00
abstract::Seventeen hominoid fossils recovered from Pliocene strata at Aramis, Middle Awash, Ethiopia make up a series comprising dental, cranial and postcranial specimens dated to around 4.4 million years ago. When compared with Australopithecus afarensis and with modern and fossil apes the Aramis fossil hominids are recognize...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/371306a0
更新日期:1994-09-22 00:00:00
abstract::A multitude of heptahelical receptors use heterotrimeric G proteins to transduce signals to specific effector target molecules. The G protein transducin, Gt, couples photon-activated rhodopsin with the effector cyclic GMP phosophodiesterase (PDE) in the vertebrate phototransduction cascade. The interactions of the Gt ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/35059138
更新日期:2001-02-22 00:00:00
abstract::Self-propagating beta-sheet-rich protein aggregates are implicated in a wide range of protein-misfolding phenomena, including amyloid diseases and prion-based inheritance. Two properties have emerged as common features of amyloids. Amyloid formation is ubiquitous: many unrelated proteins form such aggregates and even ...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature01894
更新日期:2003-08-21 00:00:00
abstract::Helium is used as a critical tracer throughout the Earth sciences, where its relatively simple isotopic systematics is used to trace degassing from the mantle, to date groundwater and to time the rise of continents. The hydrothermal system at Yellowstone National Park is famous for its high helium-3/helium-4 isotope r...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12992
更新日期:2014-02-20 00:00:00
abstract::Histoplasma capsulatum, like many other fungal pathogens, is dimorphic: it exists as mycelia in the soil and yeast in animal hosts. Because only the yeast phase is parasitic, factors which affect morphogenesis have been of interest for understanding and controlling pathogenicity. In culture, the mycelial to yeast tran...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/303806a0
更新日期:1983-06-30 00:00:00
abstract::Most Oryza sativa cultivars die within a week of complete submergence--a major constraint to rice production in south and southeast Asia that causes annual losses of over US 1 billion dollars and affects disproportionately the poorest farmers in the world. A few cultivars, such as the O. sativa ssp. indica cultivar FR...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature04920
更新日期:2006-08-10 00:00:00
abstract::Recent work has identified a neuron with widespread projections to odour processing regions of the honeybee brain whose activity represents the reward value of gustatory stimuli. We have constructed a model of bee foraging in uncertain environments based on this type of neuron and a predictive form of hebbian synaptic...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/377725a0
更新日期:1995-10-26 00:00:00
abstract::Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.1-4.8%) and effects of up to 2 centimetres per a...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature21039
更新日期:2017-02-09 00:00:00
abstract::Organisms use endogenous clocks to anticipate regular environmental cycles, such as days and tides. Natural variants resulting in differently timed behaviour or physiology, known as chronotypes in humans, have not been well characterized at the molecular level. We sequenced the genome of Clunio marinus, a marine midge...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature20151
更新日期:2016-12-01 00:00:00
abstract::The origins of religion and of complex societies represent evolutionary puzzles1-8. The 'moralizing gods' hypothesis offers a solution to both puzzles by proposing that belief in morally concerned supernatural agents culturally evolved to facilitate cooperation among strangers in large-scale societies9-13. Although pr...
journal_title:Nature
pub_type: 历史文章,杂志文章
doi:10.1038/s41586-019-1043-4
更新日期:2019-04-01 00:00:00
abstract::Crossover recombination events between homologous chromosomes are required to form chiasmata, temporary connections between homologues that ensure their proper segregation at meiosis I. Despite this requirement for crossovers and an excess of the double-strand DNA breaks that are the initiating events for meiotic reco...
journal_title:Nature
pub_type: 杂志文章
doi:10.1038/nature12577
更新日期:2013-10-31 00:00:00