Evidence map›Paper›PMID 34032640›Full record

ArticleJCI insight2021

Identification of antigen-specific TCR sequences based on biological and statistical enrichment in unselected individuals.

Neal P Smith, Bert Ruiter, Yamini V Virkud, Ang A Tu, Brinda Monian, James J Moon, J Christopher Love, Wayne G Shreffler

Open access · goldAbstract read
In one paragraph

Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
2.0field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

14 citing papers in PubMed, 21 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 1 country.

Neal P SmithCenter for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.
Bert RuiterCenter for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.
Yamini V VirkudCenter for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.
Ang A TuKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Brinda MonianKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
James J MoonCenter for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.
J Christopher LoveKoch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Wayne G ShrefflerCenter for Immunology & Inflammatory Diseases, Massachusetts General Hospital, Boston, Massachusetts, USA.
Harvard University · USMassachusetts Institute of Technology · USMassachusetts General Hospital · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI Ramnik J Xavier · 1991 to 2026
$35.3M
Tetramer CoreU19AI095261 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI XAVIER, RAMNIK J · 2011 to 2015
$10.8M
Endophenotypes of food allergy in response to oral immunotherapyK23AI130408 · NIAID · UNIV OF NORTH CAROLINA CHAPEL HILL · PI VIRKUD, YAMINI V · 2018 to 2022
$1.0M
Influx Flow CytometerS10OD016372 · OD · MASSACHUSETTS GENERAL HOSPITAL · PI PREFFER, FREDERIC IRA · 2013 to 2013
$600k
ImageStream X Analyzer 2011S10OD012027 · OD · MASSACHUSETTS GENERAL HOSPITAL · PI PREFFER, FREDERIC IRA · 2012 to 2012
$595k
Translational Immunology Core's FACSAria Cell SorterS10RR023440 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI PREFFER, FREDERIC IRA · 2008 to 2008
$500k
DEPARTMENT OF PATHOLOGY LSR2 CYTOMETER: TRANSPLANTATIONS10RR020936 · NCRR · MASSACHUSETTS GENERAL HOSPITAL · PI PREFFER, FREDERIC IRA · 2005 to 2005
$389k
NCRR NIH HHS S10 RR020936NCRR NIH HHS S10 RR023440NIAID NIH HHS K23 AI130408NIAID NIH HHS U19 AI095261NIDDK NIH HHS P30 DK043351NIH HHS S10 OD012027NIH HHS S10 OD016372
6 · The paper itself

Abstract

Recent advances in high-throughput T cell receptor (TCR) sequencing have allowed for new insights into the human TCR repertoire. However, methods for capturing antigen-specific repertoires remain an area of development. Here, we describe a potentially novel approach that utilizes both a biological and statistical enrichment to define putatively antigen-specific complementarity-determining region 3 (CDR3) repertoires in unselected individuals. The biological enrichment entailed FACS of in vitro antigen-activated memory CD4+ T cells, followed by TCRβ sequencing. The resulting TCRβ sequences were then filtered by selecting those that are statistically enriched when compared with their frequency in the autologous resting T cell compartment. Applying this method to define putatively peanut protein-specific repertoires in 27 peanut-allergic individuals resulted in a library of 7345 unique CDR3β amino acid sequences that had similar characteristics to other validated antigen-specific repertoires in terms of homology and diversity. In-depth analysis of these CDR3βs revealed 36 public sequences that demonstrated high levels of convergent recombination. In a network analysis, the public CDR3βs were shown to be core sequences with more edges than their private counterparts. This method has the potential to be applied to a wide range of T cell-mediated disorders and to yield new biomarkers and biological insights.

Indexed as

Amino Acid SequenceComplementarity Determining RegionsHigh-Throughput Nucleotide SequencingHomologous RecombinationHumansImmunologic MemoryImmunologic TestsLymphokinesPeanut HypersensitivityReceptors, Antigen, T-CellReceptors, Antigen, T-Cell, alpha-betaT-Lymphocytesantigen-specific helper factorsComplementarity Determining RegionsLymphokinesReceptors, Antigen, T-CellReceptors, Antigen, T-Cell, alpha-betaImmunologyT cell receptorT cells

Identifiers

PMID34032640
PMCPMC8410028
OpenAlexW3165860511

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.