Antibody biomarker discovery through in vitro directed evolution of consensus recognition epitopes.

Abstract:

:To enable discovery of serum antibodies indicative of disease and simultaneously develop reagents suitable for diagnosis, in vitro directed evolution was applied to identify consensus peptides recognized by patients' serum antibodies. Bacterial cell-displayed peptide libraries were quantitatively screened for binders to serum antibodies from patients with celiac disease (CD), using cell-sorting instrumentation to identify two distinct consensus epitope families specific to CD patients (PEQ and (E)/DxFV(Y)/FQ). Evolution of the (E)/DxFV(Y)/FQ consensus epitope identified a celiac-specific epitope, distinct from the two CD hallmark antigens tissue transglutaminase-2 and deamidated gliadin, exhibiting 71% sensitivity and 99% specificity (n = 231). Expansion of the first-generation PEQ consensus epitope via in vitro evolution yielded octapeptides QPEQAFPE and PFPEQxFP that identified ω- and γ-gliadins, and their deamidated forms, as immunodominant B-cell epitopes in wheat and related cereal proteins. The evolved octapeptides, but not first-generation peptides, discriminated one-way blinded CD and non-CD sera (n = 78) with exceptional accuracy, yielding 100% sensitivity and 98% specificity. Because this method, termed antibody diagnostics via evolution of peptides, does not require prior knowledge of pathobiology, it may be broadly useful for de novo discovery of antibody biomarkers and reagents for their detection.

authors

Ballew JT,Murray JA,Collin P,Mäki M,Kagnoff MF,Kaukinen K,Daugherty PS

doi

10.1073/pnas.1314792110

subject

Has Abstract

pub_date

2013-11-26 00:00:00

pages

19330-5

issue

48

eissn

0027-8424

issn

1091-6490

pii

1314792110

journal_volume

110

pub_type

杂志文章
  • Transcriptional activity of transcription factor IIE is dependent on zinc binding.

    abstract::The functions of individual basal transcription factors during the formation of an initiation complex by RNA polymerase II remain largely unknown. Transcription factor IIE (TFIIE) has recently been shown to bind to multiple targets in the initiation complex. To assess the role of zinc binding in basal transcription, w...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.91.20.9529

    authors: Maxon ME,Tjian R

    更新日期:1994-09-27 00:00:00

  • Fas (CD95) expression and death-mediating function are induced by CD4 cross-linking on CD4+ T cells.

    abstract::The CD4 receptor contributes to T-cell activation by coligating major histocompatibility complex class II on antigen presenting cells with the T-cell receptor (TCR)/CD3 complex, and triggering a cascade of signaling events including tyrosine phosphorylation of intracellular proteins. Paradoxically, CD3 cross-linking p...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.20.11014

    authors: Desbarats J,Freed JH,Campbell PA,Newell MK

    更新日期:1996-10-01 00:00:00

  • Transcription regulation of peroxisomal fatty acyl-CoA oxidase and enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase in rat liver by peroxisome proliferators.

    abstract::The structurally diverse peroxisome proliferators ciprofibrate, clofibrate, and bis(2-ethylhexyl) phthalate [(EtHx)2 greater than Pht] increase the activities of hepatic catalase and peroxisomal fatty acid beta-oxidation enzymes in conjunction with profound proliferation of peroxisomes in hepatocytes. In order to deli...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.6.1747

    authors: Reddy JK,Goel SK,Nemali MR,Carrino JJ,Laffler TG,Reddy MK,Sperbeck SJ,Osumi T,Hashimoto T,Lalwani ND

    更新日期:1986-03-01 00:00:00

  • Developmental topography of cortical thickness during infancy.

    abstract::During the first 2 postnatal years, cortical thickness of the human brain develops dynamically and spatially heterogeneously and likely peaks between 1 and 2 y of age. The striking development renders this period critical for later cognitive outcomes and vulnerable to early neurodevelopmental disorders. However, due t...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1821523116

    authors: Wang F,Lian C,Wu Z,Zhang H,Li T,Meng Y,Wang L,Lin W,Shen D,Li G

    更新日期:2019-08-06 00:00:00

  • Label-free imaging, detection, and mass measurement of single viruses by surface plasmon resonance.

    abstract::We report on label-free imaging, detection, and mass/size measurement of single viral particles in solution by high-resolution surface plasmon resonance microscopy. Diffraction of propagating plasmon waves along a metal surface by the viral particles creates images of the individual particles, which allow us to detect...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1005264107

    authors: Wang S,Shan X,Patel U,Huang X,Lu J,Li J,Tao N

    更新日期:2010-09-14 00:00:00

  • Common polymorphism in the oxytocin receptor gene (OXTR) is associated with human social recognition skills.

    abstract::The neuropeptides oxytocin and vasopressin are evolutionarily conserved regulators of social perception and behavior. Evidence is building that they are critically involved in the development of social recognition skills within rodent species, primates, and humans. We investigated whether common polymorphisms in the g...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1302985111

    authors: Skuse DH,Lori A,Cubells JF,Lee I,Conneely KN,Puura K,Lehtimäki T,Binder EB,Young LJ

    更新日期:2014-02-04 00:00:00

  • The hydrophobic moment detects periodicity in protein hydrophobicity.

    abstract::Periodicities in the polar/apolar character of the amino acid sequence of a protein can be examined by assigning to each residue a numerical hydrophobicity and searching for periodicity in the resulting one-dimensional function. The strength of each periodic component is the quantity that has been termed the hydrophob...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.1.140

    authors: Eisenberg D,Weiss RM,Terwilliger TC

    更新日期:1984-01-01 00:00:00

  • Structural and thermodynamic consequences of burial of an artificial ion pair in the hydrophobic interior of a protein.

    abstract::An artificial charge pair buried in the hydrophobic core of staphylococcal nuclease was engineered by making the V23E and L36K substitutions. Buried individually, Glu-23 and Lys-36 both titrate with pKa values near 7. When buried together their pKa values appear to be normal. The ionizable moieties of the buried Glu-L...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1402900111

    authors: Robinson AC,Castañeda CA,Schlessman JL,García-Moreno EB

    更新日期:2014-08-12 00:00:00

  • Ribonuclease BN: identification and partial characterization of a new tRNA processing enzyme.

    abstract::A new ribonuclease, RNase BN, has been identified and partially purified from a strain of Escherichia coli lacking RNase II and RNase D by using the artificial tRNA precursor tRNA-C-[14C]U as substrate. This enzyme is present in E. coli B but absent from the tRNA processing mutant strain BN which is unable to process ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.80.11.3301

    authors: Asha PK,Blouin RT,Zaniewski R,Deutscher MP

    更新日期:1983-06-01 00:00:00

  • Specification of positional information in retinal ganglion cells of Xenopus: stability of the specified state.

    abstract::In the normal development of retinotectal connections, the site in the tectum at which an optic fiber synapses is related to the position of its ganglion-cell body in the retina. How and when the ganglion cells acquire information about their positions is unknown, but the positional information that each ganglion cell...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.69.10.2860

    authors: Hunt RK,Jacobson M

    更新日期:1972-10-01 00:00:00

  • Tracking evolving communities in large linked networks.

    abstract::We are interested in tracking changes in large-scale data by periodically creating an agglomerative clustering and examining the evolution of clusters (communities) over time. We examine a large real-world data set: the NEC CiteSeer database, a linked network of >250,000 papers. Tracking changes over time requires a c...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0307750100

    authors: Hopcroft J,Khan O,Kulis B,Selman B

    更新日期:2004-04-06 00:00:00

  • Biogenesis of the pore architecture of a voltage-gated potassium channel.

    abstract::The pore domain of voltage-gated potassium (Kv) channels consists of transmembrane helices S5 and S6, the turret, the pore helix, the selectivity filter, and the loop preceding S6, with a tertiary reentrant structure between S5 and S6. Using biogenic intermediates, mass tagging (pegylation), and a molecular tape measu...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1017097108

    authors: Gajewski C,Dagcan A,Roux B,Deutsch C

    更新日期:2011-02-22 00:00:00

  • Clustered arrangement of keratin intermediate filament genes.

    abstract::We report here that component members of the keratin intermediate filament (IF) type I and type II gene families of sheep are closely linked but apparently the two families are not. Nine genes, accounting for up to half of the keratin IF gene repertoire, were mapped in four cosmid clones and the linkage between the ge...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.83.14.5048

    authors: Powell BC,Cam GR,Fietz MJ,Rogers GE

    更新日期:1986-07-01 00:00:00

  • Expression and functional significance of VE-cadherin in aggressive human melanoma cells: role in vasculogenic mimicry.

    abstract::We recently have introduced the term vasculogenic mimicry to describe the unique ability of aggressive melanoma tumor cells to form tubular structures and patterned networks in three-dimensional culture, which "mimics" embryonic vasculogenic networks formed by differentiating endothelial cells. In the current study, w...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.131209798

    authors: Hendrix MJ,Seftor EA,Meltzer PS,Gardner LM,Hess AR,Kirschmann DA,Schatteman GC,Seftor RE

    更新日期:2001-07-03 00:00:00

  • Structure of factor-inhibiting hypoxia-inducible factor 1: An asparaginyl hydroxylase involved in the hypoxic response pathway.

    abstract::Precise regulation of the evolutionarily conserved hypoxia-inducible transcription factor (HIF) ensures proper adaptation to variations in oxygen availability throughout development and into adulthood. Oxygen-dependent regulation of HIF stability and activity are mediated by hydroxylation of conserved proline and aspa...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.202614999

    authors: Dann CE 3rd,Bruick RK,Deisenhofer J

    更新日期:2002-11-26 00:00:00

  • The structural basis for the oriented assembly of a TBP/TFB/promoter complex.

    abstract::Recently the definition of the metazoan RNA polymerase II and archaeal core promoters has been expanded to include a region immediately upstream of the TATA box called the B recognition element (BRE), so named because eukaryal transcription factor TFIIB and its archaeal orthologue TFB interact with the element in a se...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.24.13668

    authors: Littlefield O,Korkhin Y,Sigler PB

    更新日期:1999-11-23 00:00:00

  • Uncovering space-independent communities in spatial networks.

    abstract::Many complex systems are organized in the form of a network embedded in space. Important examples include the physical Internet infrastructure, road networks, flight connections, brain functional networks, and social networks. The effect of space on network topology has recently come under the spotlight because of the...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1018962108

    authors: Expert P,Evans TS,Blondel VD,Lambiotte R

    更新日期:2011-05-10 00:00:00

  • Structural mechanism of sensing long dsRNA via a noncatalytic domain in human oligoadenylate synthetase 3.

    abstract::The mammalian innate immune system uses several sensors of double-stranded RNA (dsRNA) to develop the interferon response. Among these sensors are dsRNA-activated oligoadenylate synthetases (OAS), which produce signaling 2',5'-linked RNA molecules (2-5A) that activate regulated RNA decay in mammalian tissues. Differen...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1419409112

    authors: Donovan J,Whitney G,Rath S,Korennykh A

    更新日期:2015-03-31 00:00:00

  • Enzymatic transformation of nonfood biomass to starch.

    abstract::The global demand for food could double in another 40 y owing to growth in the population and food consumption per capita. To meet the world's future food and sustainability needs for biofuels and renewable materials, the production of starch-rich cereals and cellulose-rich bioenergy plants must grow substantially whi...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1302420110

    authors: You C,Chen H,Myung S,Sathitsuksanoh N,Ma H,Zhang XZ,Li J,Zhang YH

    更新日期:2013-04-30 00:00:00

  • Structural evidence for evolution of shark Ig new antigen receptor variable domain antibodies from a cell-surface receptor.

    abstract::The Ig new antigen receptors (IgNARs) are single-domain antibodies found in the serum of sharks. Here, we report 2.2- and 2.8-A structures of the type 2 IgNAR variable domains 12Y-1 and 12Y-2. Structural features include, first, an Ig superfamily topology transitional between cell adhesion molecules, antibodies, and T...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0403509101

    authors: Streltsov VA,Varghese JN,Carmichael JA,Irving RA,Hudson PJ,Nuttall SD

    更新日期:2004-08-24 00:00:00

  • Nitrifier adaptation to low energy flux controls inventory of reduced nitrogen in the dark ocean.

    abstract::Ammonia oxidation to nitrite and its subsequent oxidation to nitrate provides energy to the two populations of nitrifying chemoautotrophs in the energy-starved dark ocean, driving a coupling between reduced inorganic nitrogen (N) pools and production of new organic carbon (C) in the dark ocean. However, the relationsh...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1912367117

    authors: Zhang Y,Qin W,Hou L,Zakem EJ,Wan X,Zhao Z,Liu L,Hunt KA,Jiao N,Kao SJ,Tang K,Xie X,Shen J,Li Y,Chen M,Dai X,Liu C,Deng W,Dai M,Ingalls AE,Stahl DA,Herndl GJ

    更新日期:2020-03-03 00:00:00

  • Two alpha heavy chain disease proteins with different genomic deletions demonstrate that nonexpressed alpha heavy chain genes contain methylated bases.

    abstract::Two independently arising alpha heavy chain mutants have been found to synthesize heavy chains with CH1 deletions of approximately equal extent. Both were isolated from heavy chain-producing variants of the mouse myeloma W3129 and demonstrate that it is possible to arrive at the heavy chain disease phenotype by the pa...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.78.11.7091

    authors: Dackowski W,Morrison SL

    更新日期:1981-11-01 00:00:00

  • Functional analysis of a palindromic sequence required for normal replication of several staphylococcal plasmids.

    abstract::Most small multicopy antibiotic-resistance plasmids of Staphylococcus aureus contain a major axis of hyphenated dyad symmetry (palA) that is required for normal replication and stability, although located outside of the minimal replicon. Rearrangements affecting palA cause plasmid instability, a marked reduction in co...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.84.8.2165

    authors: Gruss AD,Ross HF,Novick RP

    更新日期:1987-04-01 00:00:00

  • Zinc folds the N-terminal domain of HIV-1 integrase, promotes multimerization, and enhances catalytic activity.

    abstract::The N-terminal domain of HIV-1 integrase contains a pair of His and Cys residues (the HHCC motif) that are conserved among retroviral integrases. Although His and Cys residues are often involved in binding zinc, the HHCC motif does not correspond to any recognized class of zinc binding domain. We have investigated the...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.93.24.13659

    authors: Zheng R,Jenkins TM,Craigie R

    更新日期:1996-11-26 00:00:00

  • Liver uptake of chylomicron remnants with high and low apoprotein E:C ratios.

    abstract::The ability of the isolated perfused rat liver to differentiate between chylomicrons and remnants with either high or low apoprotein E:C ratios was investigated. Remnants were prepared in hepatectomized rats injected with chylomicrons double-labeled with [3H]cholesterol and 14C-labeled fatty acids. By densitometric sc...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.81.18.5863

    authors: Borensztajn J,Kotlar TJ

    更新日期:1984-09-01 00:00:00

  • Crystal structure of HLA-G: a nonclassical MHC class I molecule expressed at the fetal-maternal interface.

    abstract::HLA-G is a nonclassical major histocompatibility complex class I (MHC-I) molecule that is primarily expressed at the fetal-maternal interface, where it is thought to play a role in protecting the fetus from the maternal immune response. HLA-G binds a limited repertoire of peptides and interacts with the inhibitory leu...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0409676102

    authors: Clements CS,Kjer-Nielsen L,Kostenko L,Hoare HL,Dunstone MA,Moses E,Freed K,Brooks AG,Rossjohn J,McCluskey J

    更新日期:2005-03-01 00:00:00

  • A molecular switch that governs mitochondrial fusion and fission mediated by the BCL2-like protein CED-9 of Caenorhabditis elegans.

    abstract::Depending on the cellular context, BCL2-like proteins promote mitochondrial fusion or fission. What determines which of these two opposing processes they promote has so far been unknown. Furthermore, the mechanisms through which BCL2-like proteins affect mitochondrial dynamics remain to be fully understood. The BCL2-l...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.1103218108

    authors: Lu Y,Rolland SG,Conradt B

    更新日期:2011-10-11 00:00:00

  • Blockade of beta 1- but not of beta 2-adrenergic receptors replicates propranolol's suppression of the cerebral spread of an engram in mice.

    abstract::Bitemporal injections of puromycin that primarily affect the hippocampal-entorhinal area induce amnesia of aversive maze-learning in mice for 3 days after training but are ineffective 6 or more days after training. At these later times, additional puromycin sites covering widespread forebrain areas are necessary to in...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.82.21.7458

    authors: Flexner JB,Flexner LB,Church AC,Rainbow TC,Brunswick DJ

    更新日期:1985-11-01 00:00:00

  • Thioredoxin is required for S-nitrosation of procaspase-3 and the inhibition of apoptosis in Jurkat cells.

    abstract::S-nitrosation is a posttranslational, oxidative addition of NO to cysteine residues of proteins that has been proposed as a cGMP-independent signaling pathway [Hess DT, Matsumoto A, Kim SO, Marshall HE, Stamler JS (2005) Nat Rev Mol Cell Biol 6:150-166]. A paradox of S-nitrosation is that only a small set of reactive ...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.0704898104

    authors: Mitchell DA,Morton SU,Fernhoff NB,Marletta MA

    更新日期:2007-07-10 00:00:00

  • Tumor-targeted IL-2 amplifies T cell-mediated immune response induced by gene therapy with single-chain IL-12.

    abstract::Induction, maintenance, and amplification of tumor-protective immunity after cytokine gene therapy is essential for the clinical success of immunotherapeutic approaches. We investigated whether this could be achieved by single-chain IL-12 (scIL-12) gene therapy followed by tumor-targeted IL-2 using a fusion protein co...

    journal_title:Proceedings of the National Academy of Sciences of the United States of America

    pub_type: 杂志文章

    doi:10.1073/pnas.96.15.8591

    authors: Lode HN,Xiang R,Duncan SR,Theofilopoulos AN,Gillies SD,Reisfeld RA

    更新日期:1999-07-20 00:00:00