Somatic mutation hotspots correlate with DNA polymerase eta error spectrum.

Abstract:

:Mutational spectra analysis of 15 immunoglobulin genes suggested that consensus motifs RGYW and WA were universal descriptors of somatic hypermutation. Highly mutable sites, "hotspots", that matched WA were preferentially found in one DNA strand and RGYW hotspots were found in both strands. Analysis of base-substitution hotspots in DNA polymerase error spectra showed that 33 of 36 hotspots in the human polymerase eta spectrum conformed to the WA consensus. This and four other characteristics of polymerase eta substitution specificity suggest that errors introduced by this enzyme during synthesis of the nontranscribed DNA strand in variable regions may contribute to strand-specific somatic hypermutagenesis of immunoglobulin genes at A-T base pairs.

journal_name

Nat Immunol

journal_title

Nature immunology

authors

Rogozin IB,Pavlov YI,Bebenek K,Matsuda T,Kunkel TA

doi

10.1038/88732

keywords:

subject

Has Abstract

pub_date

2001-06-01 00:00:00

pages

530-6

issue

6

eissn

1529-2908

issn

1529-2916

pii

88732

journal_volume

2

pub_type

杂志文章
  • Stimulation of CD25(+)CD4(+) regulatory T cells through GITR breaks immunological self-tolerance.

    abstract::CD25(+)CD4(+) regulatory T cells in normal animals are engaged in the maintenance of immunological self-tolerance. We show here that glucocorticoid-induced tumor necrosis factor receptor family-related gene (GITR, also known as TNFRSF18)--a member of the tumor necrosis factor-nerve growth factor (TNF-NGF) receptor gen...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni759

    authors: Shimizu J,Yamazaki S,Takahashi T,Ishida Y,Sakaguchi S

    更新日期:2002-02-01 00:00:00

  • Inducible degradation of lncRNA Sros1 promotes IFN-γ-mediated activation of innate immune responses by stabilizing Stat1 mRNA.

    abstract::Interferon-γ (IFN-γ) is essential for the innate immune response to intracellular bacteria. Noncoding RNAs and RNA-binding proteins (RBPs) need to be further considered in studies of regulation of the IFN-γ-activated signaling pathway in macrophages. In the present study, we found that the microRNA miR-1 promoted IFN-...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-019-0542-7

    authors: Xu H,Jiang Y,Xu X,Su X,Liu Y,Ma Y,Zhao Y,Shen Z,Huang B,Cao X

    更新日期:2019-12-01 00:00:00

  • Mechanosensing through immunoreceptors.

    abstract::The immune response is orchestrated by a variety of immune cells. The function of each cell is determined by the collective signals from various immunoreceptors, whose expression and activity depend on the developmental stages of the cell and its environmental context. Recent studies have highlighted the presence of m...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-019-0491-1

    authors: Zhu C,Chen W,Lou J,Rittase W,Li K

    更新日期:2019-10-01 00:00:00

  • Intrahepatic myeloid-cell aggregates enable local proliferation of CD8(+) T cells and successful immunotherapy against chronic viral liver infection.

    abstract::Chronic infection is difficult to overcome because of exhaustion or depletion of cytotoxic effector CD8(+) T cells (cytotoxic T lymphoytes (CTLs)). Here we report that signaling via Toll-like receptors (TLRs) induced intrahepatic aggregates of myeloid cells that enabled the population expansion of CTLs (iMATEs: 'intra...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2573

    authors: Huang LR,Wohlleber D,Reisinger F,Jenne CN,Cheng RL,Abdullah Z,Schildberg FA,Odenthal M,Dienes HP,van Rooijen N,Schmitt E,Garbi N,Croft M,Kurts C,Kubes P,Protzer U,Heikenwalder M,Knolle PA

    更新日期:2013-06-01 00:00:00

  • The transcription factor ATF7 mediates lipopolysaccharide-induced epigenetic changes in macrophages involved in innate immunological memory.

    abstract::Immunological memory is thought to be mediated exclusively by lymphocytes. However, enhanced innate immune responses caused by a previous infection increase protection against reinfection, which suggests the presence of innate immunological memory. Here we identified an important role for the stress-response transcrip...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3257

    authors: Yoshida K,Maekawa T,Zhu Y,Renard-Guillet C,Chatton B,Inoue K,Uchiyama T,Ishibashi K,Yamada T,Ohno N,Shirahige K,Okada-Hatakeyama M,Ishii S

    更新日期:2015-10-01 00:00:00

  • The immunological synapse and the actin cytoskeleton: molecular hardware for T cell signaling.

    abstract::The actin cytoskeleton seems to play two critical roles in the activation of T cells. One of these roles is T cell shape development and movement, including formation of the immunological synapse. The other is the formation of a scaffold for signaling components. This review focuses on the recent convergence of cell b...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/76877

    authors: Dustin ML,Cooper JA

    更新日期:2000-07-01 00:00:00

  • IL-1 induces mitochondrial translocation of IRAK2 to suppress oxidative metabolism in adipocytes.

    abstract::Chronic inflammation is a common feature of obesity, with elevated cytokines such as interleukin-1 (IL-1) in the circulation and tissues. Here, we report an unconventional IL-1R-MyD88-IRAK2-PHB/OPA1 signaling axis that reprograms mitochondrial metabolism in adipocytes to exacerbate obesity. IL-1 induced recruitment of...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-020-0750-1

    authors: Zhou H,Wang H,Yu M,Schugar RC,Qian W,Tang F,Liu W,Yang H,McDowell RE,Zhao J,Gao J,Dongre A,Carman JA,Yin M,Drazba JA,Dent R,Hine C,Chen YR,Smith JD,Fox PL,Brown JM,Li X

    更新日期:2020-10-01 00:00:00

  • High-density lipoprotein mediates anti-inflammatory reprogramming of macrophages via the transcriptional regulator ATF3.

    abstract::High-density lipoprotein (HDL) mediates reverse cholesterol transport and is known to be protective against atherosclerosis. In addition, HDL has potent anti-inflammatory properties that may be critical for protection against other inflammatory diseases. The molecular mechanisms of how HDL can modulate inflammation, p...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2784

    authors: De Nardo D,Labzin LI,Kono H,Seki R,Schmidt SV,Beyer M,Xu D,Zimmer S,Lahrmann C,Schildberg FA,Vogelhuber J,Kraut M,Ulas T,Kerksiek A,Krebs W,Bode N,Grebe A,Fitzgerald ML,Hernandez NJ,Williams BR,Knolle P,Kneillin

    更新日期:2014-02-01 00:00:00

  • CD160 inhibits activation of human CD4+ T cells through interaction with herpesvirus entry mediator.

    abstract::CD160, a glycosylphosphatidylinositol-anchored member of the immunoglobulin superfamily, is expressed on both cytolytic lymphocytes and some unstimulated CD4+ T cells. Here we show that CD160 expression was increased after activation of human CD4+ T cells and that crosslinking CD160 with monoclonal antibody strongly i...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1554

    authors: Cai G,Anumanthan A,Brown JA,Greenfield EA,Zhu B,Freeman GJ

    更新日期:2008-02-01 00:00:00

  • The transcriptional regulator Aire coopts the repressive ATF7ip-MBD1 complex for the induction of immunotolerance.

    abstract::The maintenance of immunological tolerance requires the deletion of self-reactive T cells in the thymus. The expression of genes encoding tissue-specific antigens (TSAs) by thymic epithelial cells is critical for this process and depends on activity of the transcriptional regulator Aire; however, the molecular mechani...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2820

    authors: Waterfield M,Khan IS,Cortez JT,Fan U,Metzger T,Greer A,Fasano K,Martinez-Llordella M,Pollack JL,Erle DJ,Su M,Anderson MS

    更新日期:2014-03-01 00:00:00

  • Different molecular complexes that mediate transcriptional induction and repression by FoxP3.

    abstract::FoxP3 conditions the transcriptional signature and functional facets of regulatory T cells (Treg cells). Its mechanism of action, whether as an activator or a repressor, has remained unclear. Here, chromatin analysis showed that FoxP3 bound active enhancer elements, not repressed chromatin, around loci over- or under-...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.3835

    authors: Kwon HK,Chen HM,Mathis D,Benoist C

    更新日期:2017-11-01 00:00:00

  • Individual stem cells with highly variable proliferation and self-renewal properties comprise the human hematopoietic stem cell compartment.

    abstract::Hematopoiesis requires tight regulation of the hematopoietic stem cell (HSC) population; however, the dynamics of HSC use at steady state are uncertain. Over 3-7 months, we evaluated the repopulation and self-renewal of more than 600 individual human 'severe combined immunodeficiency mouse-repopulating cells' (SRCs), ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1393

    authors: McKenzie JL,Gan OI,Doedens M,Wang JC,Dick JE

    更新日期:2006-11-01 00:00:00

  • Second signals rescue B cells from activation-induced mitochondrial dysfunction and death.

    abstract::B cells are activated by two temporally distinct signals, the first provided by the binding of antigen to the B cell antigen receptor (BCR), and the second provided by helper T cells. Here we found that B cells responded to antigen by rapidly increasing their metabolic activity, including both oxidative phosphorylatio...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-018-0156-5

    authors: Akkaya M,Traba J,Roesler AS,Miozzo P,Akkaya B,Theall BP,Sohn H,Pena M,Smelkinson M,Kabat J,Dahlstrom E,Dorward DW,Skinner J,Sack MN,Pierce SK

    更新日期:2018-08-01 00:00:00

  • A critical function for TGF-beta signaling in the development of natural CD4+CD25+Foxp3+ regulatory T cells.

    abstract::The molecular mechanisms directing the development of 'natural' CD4+CD25+Foxp3+ regulatory T cells (T(reg) cells) in the thymus are not thoroughly understood. We show here that conditional deletion of transforming growth factor-beta receptor I (TbetaRI) in T cells blocked the appearance of CD4+CD25+Foxp3+ thymocytes a...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1607

    authors: Liu Y,Zhang P,Li J,Kulkarni AB,Perruche S,Chen W

    更新日期:2008-06-01 00:00:00

  • CEACAM1 inhibits Toll-like receptor 2-triggered antibacterial responses of human pulmonary epithelial cells.

    abstract::Although Moraxella catarrhalis and Neisseria meningitidis are important human pathogens, they often colonize the human respiratory tract without causing overt clinical symptoms. Both pathogens express structurally unrelated proteins that share the ability to stimulate the adhesion molecule CEACAM1 expressed on human c...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1661

    authors: Slevogt H,Zabel S,Opitz B,Hocke A,Eitel J,N'guessan PD,Lucka L,Riesbeck K,Zimmermann W,Zweigner J,Temmesfeld-Wollbrueck B,Suttorp N,Singer BB

    更新日期:2008-11-01 00:00:00

  • Duration of TCR signaling controls CD4-CD8 lineage differentiation in vivo.

    abstract::The duration of T cell receptor (TCR) signaling is thought to be important for thymocyte differentiation into the CD4 or CD8 lineage. However, the in vivo relevance of this hypothesis is unclear. Here we divided T cell positive selection into genetically separable developmental steps by confining TCR signal transducti...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1040

    authors: Liu X,Bosselut R

    更新日期:2004-03-01 00:00:00

  • Id2 and Id3 maintain the regulatory T cell pool to suppress inflammatory disease.

    abstract::Regulatory T (Treg) cells suppress the development of inflammatory disease, but our knowledge of transcriptional regulators that control this function remains incomplete. Here we show that expression of Id2 and Id3 in Treg cells was required to suppress development of fatal inflammatory disease. We found that T cell a...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2928

    authors: Miyazaki M,Miyazaki K,Chen S,Itoi M,Miller M,Lu LF,Varki N,Chang AN,Broide DH,Murre C

    更新日期:2014-08-01 00:00:00

  • PTEN functions to 'prioritize' chemotactic cues and prevent 'distraction' in migrating neutrophils.

    abstract::Neutrophils encounter and 'prioritize' many chemoattractants in their pursuit of bacteria. Here we tested the possibility that the phosphatase PTEN is responsible for the prioritization of chemoattractants. Neutrophils induced chemotaxis by two separate pathways, the phosphatidylinositol-3-OH kinase (PI(3)K) phosphata...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1623

    authors: Heit B,Robbins SM,Downey CM,Guan Z,Colarusso P,Miller BJ,Jirik FR,Kubes P

    更新日期:2008-07-01 00:00:00

  • Structural evidence for a germline-encoded T cell receptor-major histocompatibility complex interaction 'codon'.

    abstract::All complexes of T cell receptors (TCRs) bound to peptide-major histocompatibility complex (pMHC) molecules assume a stereotyped binding 'polarity', despite wide variations in TCR-pMHC docking angles. However, existing TCR-pMHC crystal structures have failed to show broadly conserved pairwise interaction motifs. Here ...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1502

    authors: Feng D,Bond CJ,Ely LK,Maynard J,Garcia KC

    更新日期:2007-09-01 00:00:00

  • HIV-AIDS: much accomplished, much to do.

    abstract::As a result of decades of research-driven breakthroughs in basic and clinical science and recent advances in the broad-scale implementation of interventions for the prevention and treatment of infection with HIV, a turning point has been reached in the global HIV-AIDS pandemic. To end the pandemic and achieve the goal...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2735

    authors: Fauci AS,Folkers GK,Dieffenbach CW

    更新日期:2013-11-01 00:00:00

  • Regulation of lymphocyte development by Notch signaling.

    abstract::Notch molecules are well conserved from Drosophila melanogaster to mammals and regulate a broad spectrum of various cell lineage commitment processes. Recent studies using inhibitors, transgenic mice and conditional loss-of-function approaches have demonstrated essential roles for Notch signaling in the differentiatio...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni1453

    authors: Tanigaki K,Honjo T

    更新日期:2007-05-01 00:00:00

  • Alarmin S100A11 initiates a chemokine response to the human pathogen Toxoplasma gondii.

    abstract::Toxoplasma gondii is a common protozoan parasite that infects up to one third of the world's population. Notably, very little is known about innate immune sensing mechanisms for this obligate intracellular parasite by human cells. Here, by applying an unbiased biochemical screening approach, we show that human monocyt...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/s41590-018-0250-8

    authors: Safronova A,Araujo A,Camanzo ET,Moon TJ,Elliott MR,Beiting DP,Yarovinsky F

    更新日期:2019-01-01 00:00:00

  • Protein-glycan interactions in the control of innate and adaptive immune responses.

    abstract::The importance of protein glycosylation in the migration of immune cells throughout the body has been extensively appreciated. However, our awareness of the impact of glycosylation on the regulation of innate and adaptive immune responses is relatively new. An increasing number of studies reveal the relevance of glyco...

    journal_title:Nature immunology

    pub_type: 杂志文章,评审

    doi:10.1038/ni.f.203

    authors: van Kooyk Y,Rabinovich GA

    更新日期:2008-06-01 00:00:00

  • Production of an antigenic peptide by insulin-degrading enzyme.

    abstract::Most antigenic peptides presented by major histocompatibility complex (MHC) class I molecules are produced by the proteasome. Here we show that a proteasome-independent peptide derived from the human tumor protein MAGE-A3 is produced directly by insulin-degrading enzyme (IDE), a cytosolic metallopeptidase. Cytotoxic T...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1862

    authors: Parmentier N,Stroobant V,Colau D,de Diesbach P,Morel S,Chapiro J,van Endert P,Van den Eynde BJ

    更新日期:2010-05-01 00:00:00

  • Sensing and alarm function of resident memory CD8⁺ T cells.

    abstract::CD8(+) T cells eliminate intracellular infections through two contact-dependent effector functions: cytolysis and secretion of antiviral cytokines. Here we identify the following additional function for memory CD8(+) T cells that persist at front-line sites of microbial exposure: to serve as local sensors of previousl...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.2568

    authors: Schenkel JM,Fraser KA,Vezys V,Masopust D

    更新日期:2013-05-01 00:00:00

  • The Drosophila immune system detects bacteria through specific peptidoglycan recognition.

    abstract::The Drosophila immune system discriminates between different classes of infectious microbes and responds with pathogen-specific defense reactions through selective activation of the Toll and the immune deficiency (Imd) signaling pathways. The Toll pathway mediates most defenses against Gram-positive bacteria and fungi...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni922

    authors: Leulier F,Parquet C,Pili-Floury S,Ryu JH,Caroff M,Lee WJ,Mengin-Lecreulx D,Lemaitre B

    更新日期:2003-05-01 00:00:00

  • Activation of the NLRP3 inflammasome by islet amyloid polypeptide provides a mechanism for enhanced IL-1β in type 2 diabetes.

    abstract::Interleukin 1β (IL-1β) is an important inflammatory mediator of type 2 diabetes. Here we show that oligomers of islet amyloid polypeptide (IAPP), a protein that forms amyloid deposits in the pancreas during type 2 diabetes, triggered the NLRP3 inflammasome and generated mature IL-1β. One therapy for type 2 diabetes, g...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni.1935

    authors: Masters SL,Dunne A,Subramanian SL,Hull RL,Tannahill GM,Sharp FA,Becker C,Franchi L,Yoshihara E,Chen Z,Mullooly N,Mielke LA,Harris J,Coll RC,Mills KH,Mok KH,Newsholme P,Nuñez G,Yodoi J,Kahn SE,Lavelle EC,O'Neill

    更新日期:2010-10-01 00:00:00

  • Regulation of naive T cell function by the NF-kappaB2 pathway.

    abstract::T cell activation involves the orchestration of several signaling pathways, including that of the 'classical' transcription factor NF-kappaB components NF-kappaB1-RelA. The function of the 'nonclassical' NF-kappaB2-RelB pathway is less clear, although T cells lacking components of this pathway have activation defects....

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1351

    authors: Ishimaru N,Kishimoto H,Hayashi Y,Sprent J

    更新日期:2006-07-01 00:00:00

  • Author Correction: Alveolar macrophages are epigenetically altered after inflammation, leading to long-term lung immunoparalysis.

    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 immunology

    pub_type: 已发布勘误

    doi:10.1038/s41590-020-0739-9

    authors: Roquilly A,Jacqueline C,Davieau M,Mollé A,Sadek A,Fourgeux C,Rooze P,Broquet A,Misme-Aucouturier B,Chaumette T,Vourc'h M,Cinotti R,Marec N,Gauttier V,McWilliam HEG,Altare F,Poschmann J,Villadangos JA,Asehnoune K

    更新日期:2020-08-01 00:00:00

  • Regulation of interleukin 7-dependent immunoglobulin heavy-chain variable gene rearrangements by transcription factor STAT5.

    abstract::Rearrangement of immunoglobulin heavy-chain variable (V(H)) gene segments has been suggested to be regulated by interleukin 7 signaling in pro-B cells. However, the genetic evidence for this recombination pathway has been challenged. Furthermore, no molecular components that directly control V(H) gene rearrangement ha...

    journal_title:Nature immunology

    pub_type: 杂志文章

    doi:10.1038/ni1226

    authors: Bertolino E,Reddy K,Medina KL,Parganas E,Ihle J,Singh H

    更新日期:2005-08-01 00:00:00