Progression of autoimmune diabetes driven by avidity maturation of a T-cell population.

Abstract:

:For unknown reasons, autoimmune diseases such as type 1 diabetes develop after prolonged periods of inflammation of mononuclear cells in target tissues. Here we show that progression of pancreatic islet inflammation to overt diabetes in nonobese diabetic (NOD) mice is driven by the 'avidity maturation' of a prevailing, pancreatic beta-cell-specific T-lymphocyte population carrying the CD8 antigen. This T-lymphocyte population recognizes two related peptides (NRP and NRP-A7) in the context of H-2Kd class I molecules of the major histocompatibility complex (MHC). As pre-diabetic NOD mice age, their islet-associated CD8+ T lymphocytes contain increasing numbers of NRP-A7-reactive cells, and these cells bind NRP-A7/H-2Kd tetramers with increased specificity, increased avidity and longer half-lives. Repeated treatment of pre-diabetic NOD mice with soluble NRP-A7 peptide blunts the avidity maturation of the NRP-A7-reactive CD8+ T-cell population by selectively deleting those clonotypes expressing T-cell receptors with the highest affinity and lowest dissociation rates for peptide-MHC binding. This inhibits the local production of T cells that are cytotoxic to beta cells, and halts the progression from severe insulitis to diabetes. We conclude that avidity maturation of pathogenic T-cell populations may be the key event in the progression of benign inflammation to overt disease in autoimmunity.

journal_name

Nature

journal_title

Nature

authors

Amrani A,Verdaguer J,Serra P,Tafuro S,Tan R,Santamaria P

doi

10.1038/35021081

keywords:

subject

Has Abstract

pub_date

2000-08-17 00:00:00

pages

739-42

issue

6797

eissn

0028-0836

issn

1476-4687

journal_volume

406

pub_type

杂志文章

相关文献

NATURE文献大全
  • Cloning and sequence analysis of cDNAs encoding two distinct somatostatin precursors found in the endocrine pancreas of anglerfish.

    abstract::Complementary DNAs for two distinct anglerfish somatostatin peptides (termed I and II) have been cloned in bacterial plasmids and sequenced. The nucleotide sequence for somatostatin I encodes a large percursor peptide (molecular weight 13,300) in which the somatostatin hormones is at the carboxyl terminus. The predict...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/288137a0

    authors: Hobart P,Crawford R,Shen L,Pictet R,Rutter WJ

    更新日期:1980-11-13 00:00:00

  • Horizontal endosymbiont transmission in hydrothermal vent tubeworms.

    abstract::Transmission of obligate bacterial symbionts between generations is vital for the survival of the host. Although the larvae of certain hydrothermal vent tubeworms (Vestimentifera, Siboglinidae) are symbiont-free and possess a transient digestive system, these structures are lost during development, resulting in adult ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature04793

    authors: Nussbaumer AD,Fisher CR,Bright M

    更新日期:2006-05-18 00:00:00

  • Oceanic forcing of penultimate deglacial and last interglacial sea-level rise.

    abstract::Sea-level histories during the two most recent deglacial-interglacial intervals show substantial differences1-3 despite both periods undergoing similar changes in global mean temperature4,5 and forcing from greenhouse gases6. Although the last interglaciation (LIG) experienced stronger boreal summer insolation forcing...

    journal_title:Nature

    pub_type: 历史文章,杂志文章

    doi:10.1038/s41586-020-1931-7

    authors: Clark PU,He F,Golledge NR,Mitrovica JX,Dutton A,Hoffman JS,Dendy S

    更新日期:2020-01-01 00:00:00

  • Potentiation of neuroblastoma metastasis by loss of caspase-8.

    abstract::Neuroblastoma, the most common paediatric solid tumour, arises from defective neural crest cells. Genetic alterations occur frequently in the most aggressive neuroblastomas. In particular, deletion or suppression of the proapoptotic enzyme caspase-8 is common in malignant, disseminated disease, although the effect of ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature04323

    authors: Stupack DG,Teitz T,Potter MD,Mikolon D,Houghton PJ,Kidd VJ,Lahti JM,Cheresh DA

    更新日期:2006-01-05 00:00:00

  • Securin-independent regulation of separase by checkpoint-induced shugoshin-MAD2.

    abstract::Separation of eukaryotic sister chromatids during the cell cycle is timed by the spindle assembly checkpoint (SAC) and ultimately triggered when separase cleaves cohesion-mediating cohesin1-3. Silencing of the SAC during metaphase activates the ubiquitin ligase APC/C (anaphase-promoting complex, also known as the cycl...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/s41586-020-2182-3

    authors: Hellmuth S,Gómez-H L,Pendás AM,Stemmann O

    更新日期:2020-04-01 00:00:00

  • Antibodies against metal chelates.

    abstract::Because monoclonal antibodies can recognize and bind to specific groups of atoms such as tumour antigens, they have promise for use in vivo as carriers of radionuclides, drugs or other appended molecules for diagnosis and treatment of disease. Attachment of metal ions to antibodies by means of bifunctional chelating a...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/316265a0

    authors: Reardan DT,Meares CF,Goodwin DA,McTigue M,David GS,Stone MR,Leung JP,Bartholomew RM,Frincke JM

    更新日期:1985-07-18 00:00:00

  • Embryonic acetylcholine receptors guarantee spontaneous contractions in rat developing muscle.

    abstract::Many proteins are expressed in distinct embryonic and adult forms. However, in most cases we do not know why the embryonic form of proteins is required. This question can be readily addressed for the acetylcholine receptor (AChR) because developmentally specified modifications of this ligand-gated ion channel can be d...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/335066a0

    authors: Jaramillo F,Vicini S,Schuetze SM

    更新日期:1988-09-01 00:00:00

  • Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis.

    abstract::Coronavirus disease 2019 (COVID-19) is a disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and has resulted in a pandemic1. The C5a complement factor and its receptor C5aR1 (also known as CD88) have a key role in the initiation and maintenance of several inflammatory respons...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/s41586-020-2600-6

    authors: Carvelli J,Demaria O,Vély F,Batista L,Chouaki Benmansour N,Fares J,Carpentier S,Thibult ML,Morel A,Remark R,André P,Represa A,Piperoglou C,Explore COVID-19 IPH group.,Explore COVID-19 Marseille Immunopole group.,Cordier PY

    更新日期:2020-12-01 00:00:00

  • Monophyletic origin of Lake Victoria cichlid fishes suggested by mitochondrial DNA sequences.

    abstract::Lake Victoria, together with its satellite lakes, harbours roughly 200 endemic forms of cichlid fishes that are classified as 'haplochromines' and yet the lake system is less than a million years old. This 'flock' has attracted attention because of the possibility that it evolved within the lake from one ancestral spe...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/347550a0

    authors: Meyer A,Kocher TD,Basasibwaki P,Wilson AC

    更新日期:1990-10-11 00:00:00

  • Discovery and saturation analysis of cancer genes across 21 tumour types.

    abstract::Although a few cancer genes are mutated in a high proportion of tumours of a given type (>20%), most are mutated at intermediate frequencies (2-20%). To explore the feasibility of creating a comprehensive catalogue of cancer genes, we analysed somatic point mutations in exome sequences from 4,742 human cancers and the...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature12912

    authors: Lawrence MS,Stojanov P,Mermel CH,Robinson JT,Garraway LA,Golub TR,Meyerson M,Gabriel SB,Lander ES,Getz G

    更新日期:2014-01-23 00:00:00

  • Polarization rotation mechanism for ultrahigh electromechanical response in single-crystal piezoelectrics

    abstract::Piezoelectric materials, which convert mechanical to electrical energy (and vice versa), are crucial in medical imaging, telecommunication and ultrasonic devices. A new generation of single-crystal materials, such as Pb(Zn1/3Nb2/3)O3-PbTiO3 (PZN-PT) and Pb(Mg1/3Nb2/3)O3-PbTiO3 (PMN-PT), exhibit a piezoelectric effect ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/35002022

    authors: Fu H,Cohen RE

    更新日期:2000-01-20 00:00:00

  • Messenger RNA from human brain induces drug- and voltage-operated channels in Xenopus oocytes.

    abstract::Sodium channels and receptors to serotonin and kainate were 'transplanted' from human brain into frog oocytes, by isolating messenger RNA from a fetal brain, and injecting it into Xenopus laevis oocytes. The mRNA was translated by the oocyte and induced the appearance of functional receptors and channels in its membra...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/308421a0

    authors: Gundersen CB,Miledi R,Parker I

    更新日期:1984-03-29 00:00:00

  • Interpretation of the sonic hedgehog morphogen gradient by a temporal adaptation mechanism.

    abstract::Morphogens act in developing tissues to control the spatial arrangement of cellular differentiation. The activity of a morphogen has generally been viewed as a concentration-dependent response to a diffusible signal, but the duration of morphogen signalling can also affect cellular responses. One such example is the m...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature06347

    authors: Dessaud E,Yang LL,Hill K,Cox B,Ulloa F,Ribeiro A,Mynett A,Novitch BG,Briscoe J

    更新日期:2007-11-29 00:00:00

  • Structural determinants for regulation of phosphodiesterase by a G protein at 2.0 A.

    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

    authors: Slep KC,Kercher MA,He W,Cowan CW,Wensel TG,Sigler PB

    更新日期:2001-02-22 00:00:00

  • Structure of a C-type mannose-binding protein complexed with an oligosaccharide.

    abstract::C-type (Ca(2+)-dependent) animal lectins such as mannose-binding proteins mediate many cell-surface carbohydrate-recognition events. The crystal structure at 1.7 A resolution of the carbohydrate-recognition domain of rat mannose-binding protein complexed with an oligomannose asparaginyl-oligosaccharide reveals that Ca...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/360127a0

    authors: Weis WI,Drickamer K,Hendrickson WA

    更新日期:1992-11-12 00:00:00

  • Genome-wide analysis identifies NR4A1 as a key mediator of T cell dysfunction.

    abstract::T cells become dysfunctional when they encounter self antigens or are exposed to chronic infection or to the tumour microenvironment1. The function of T cells is tightly regulated by a combinational co-stimulatory signal, and dominance of negative co-stimulation results in T cell dysfunction2. However, the molecular m...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/s41586-019-0979-8

    authors: Liu X,Wang Y,Lu H,Li J,Yan X,Xiao M,Hao J,Alekseev A,Khong H,Chen T,Huang R,Wu J,Zhao Q,Wu Q,Xu S,Wang X,Jin W,Yu S,Wang Y,Wei L,Wang A,Zhong B,Ni L,Liu X,Nurieva R,Ye L,Tian Q,Bian XW,Dong C

    更新日期:2019-03-01 00:00:00

  • Crystal structure of the CusBA heavy-metal efflux complex of Escherichia coli.

    abstract::Gram-negative bacteria, such as Escherichia coli, expel toxic chemicals through tripartite efflux pumps that span both the inner and outer membrane. The three parts are an inner membrane, substrate-binding transporter; a membrane fusion protein; and an outer-membrane-anchored channel. The fusion protein connects the t...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature09743

    authors: Su CC,Long F,Zimmermann MT,Rajashankar KR,Jernigan RL,Yu EW

    更新日期:2011-02-24 00:00:00

  • A binary main-belt comet.

    abstract::Asteroids are primitive Solar System bodies that evolve both collisionally and through disruptions arising from rapid rotation. These processes can lead to the formation of binary asteroids and to the release of dust, both directly and, in some cases, through uncovering frozen volatiles. In a subset of the asteroids c...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature23892

    authors: Agarwal J,Jewitt D,Mutchler M,Weaver H,Larson S

    更新日期:2017-09-20 00:00:00

  • The mammalian sodium channel BNC1 is required for normal touch sensation.

    abstract::Of the vertebrate senses, touch is the least understood at the molecular level The ion channels that form the core of the mechanosensory complex and confer touch sensitivity remain unknown. However, the similarity of the brain sodium channel 1 (BNC1) to nematode proteins involved in mechanotransduction indicated that ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/35039512

    authors: Price MP,Lewin GR,McIlwrath SL,Cheng C,Xie J,Heppenstall PA,Stucky CL,Mannsfeldt AG,Brennan TJ,Drummond HA,Qiao J,Benson CJ,Tarr DE,Hrstka RF,Yang B,Williamson RA,Welsh MJ

    更新日期:2000-10-26 00:00:00

  • Synthesizing arbitrary quantum states in a superconducting resonator.

    abstract::The superposition principle is a fundamental tenet of quantum mechanics. It allows a quantum system to be 'in two places at the same time', because the quantum state of a physical system can simultaneously include measurably different physical states. The preparation and use of such superposed states forms the basis o...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature08005

    authors: Hofheinz M,Wang H,Ansmann M,Bialczak RC,Lucero E,Neeley M,O'Connell AD,Sank D,Wenner J,Martinis JM,Cleland AN

    更新日期:2009-05-28 00:00:00

  • Excitatory transmission from the amygdala to nucleus accumbens facilitates reward seeking.

    abstract::The basolateral amygdala (BLA) has a crucial role in emotional learning irrespective of valence. The BLA projection to the nucleus accumbens (NAc) is thought to modulate cue-triggered motivated behaviours, but our understanding of the interaction between these two brain regions has been limited by the inability to man...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature10194

    authors: Stuber GD,Sparta DR,Stamatakis AM,van Leeuwen WA,Hardjoprajitno JE,Cho S,Tye KM,Kempadoo KA,Zhang F,Deisseroth K,Bonci A

    更新日期:2011-06-29 00:00:00

  • Involvement of p34cdc2 in establishing the dependency of S phase on mitosis.

    abstract::Mutants of cdc2+ can disrupt the dependency of S phase on completion of the previous mitosis. By changing the state of p34cdc2 it is possible to reprogramme a cell from entering mitosis to undergoing S phase. This leads to the proposal that the cell cycle can be considered a p34cdc2 cycle, and has implications for the...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/349388a0

    authors: Broek D,Bartlett R,Crawford K,Nurse P

    更新日期:1991-01-31 00:00:00

  • Direct thermal neutron detection by the 2D semiconductor 6LiInP2Se6.

    abstract::Highly efficient neutron detectors are critical in many sectors, including national security1,2, medicine3, crystallography4 and astronomy5. The main neutron detection technologies currently used involve 3He-gas-filled proportional counters6 and light scintillators7 for thermalized neutrons. Semiconductors could provi...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/s41586-019-1886-8

    authors: Chica DG,He Y,McCall KM,Chung DY,Pak RO,Trimarchi G,Liu Z,De Lurgio PM,Wessels BW,Kanatzidis MG

    更新日期:2020-01-01 00:00:00

  • Proton inhibition of N-methyl-D-aspartate receptors in cerebellar neurons.

    abstract::Mammalian neurons contain at least three types of excitatory amino-acid receptors, selectively activated by N-methyl-D-aspartate (NMDA) or aspartate, (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionate ((S)-AMPA) and kainate. An important aspect of NMDA receptors is their regulation by a variety of factors such...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/345347a0

    authors: Traynelis SF,Cull-Candy SG

    更新日期:1990-05-24 00:00:00

  • High-speed countercurrent chromatography.

    abstract::Support-free high-speed countercurrent liquid chromatography provides a rich domain of applications, some beyond reach of conventional liquid chromatography. ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/326419a0

    authors: Ito Y

    更新日期:1987-03-26 00:00:00

  • Evidence for a viral superantigen in humans.

    abstract::Superantigens bind class II major histocompatibility proteins and stimulate powerful proliferative responses of T lymphocytes bearing particular V beta sequences as part of their alpha beta antigen receptor. Exogenous bacterial superantigens are responsible for food poisoning and toxic shock syndrome. Murine virus-enc...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/358507a0

    authors: Lafon M,Lafage M,Martinez-Arends A,Ramirez R,Vuillier F,Charron D,Lotteau V,Scott-Algara D

    更新日期:1992-08-06 00:00:00

  • Rescue of bicoid mutant Drosophila embryos by bicoid fusion proteins containing heterologous activating sequences.

    abstract::The maternal gene bicoid (bcd) determines pattern in the anterior half of the Drosophila embryo. It is reported here that the injection of bcd mutant embryos with messenger RNAs that encode proteins consisting of heterologous acidic transcriptional activating sequences fused to the DNA-binding portion of the bcd gene ...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/342149a0

    authors: Driever W,Ma J,Nüsslein-Volhard C,Ptashne M

    更新日期:1989-11-09 00:00:00

  • Patent views: commercialization of research.

    abstract::The first open meeting to discuss the growing issue of commercialism in academic research was convened by the New York Bar Association's patent committee. Participants included Steven Muller, president of Johns Hopkins University, Joshua Lederberg, president of Rockefeller University, and A. Thomas Bartlett, presiden...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/296792a0

    authors: Stein MD

    更新日期:1982-04-29 00:00:00

  • Somatic copy number mosaicism in human skin revealed by induced pluripotent stem cells.

    abstract::Reprogramming somatic cells into induced pluripotent stem cells (iPSCs) has been suspected of causing de novo copy number variation. To explore this issue, here we perform a whole-genome and transcriptome analysis of 20 human iPSC lines derived from the primary skin fibroblasts of seven individuals using next-generati...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/nature11629

    authors: Abyzov A,Mariani J,Palejev D,Zhang Y,Haney MS,Tomasini L,Ferrandino AF,Rosenberg Belmaker LA,Szekely A,Wilson M,Kocabas A,Calixto NE,Grigorenko EL,Huttner A,Chawarska K,Weissman S,Urban AE,Gerstein M,Vaccarino FM

    更新日期:2012-12-20 00:00:00

  • Role of interactions between the origin recognition complex and SIR1 in transcriptional silencing.

    abstract::Transcriptional silencing of the HM mating-type loci in the yeast Saccharomyces cerevisiae is caused by the localized formation of an altered chromatin structure, analogous to heterochromatin in higher eukaryotes. Silencing depends on cis-acting sequences, termed silencers, as well as several trans-acting factors, inc...

    journal_title:Nature

    pub_type: 杂志文章

    doi:10.1038/381251a0

    authors: Triolo T,Sternglanz R

    更新日期:1996-05-16 00:00:00