Evidence map›Paper›PMID 24069285›Full record

ArticlePloS one2013

Combining next-generation sequencing and immune assays: a novel method for identification of antigen-specific T cells.

Mark Klinger, Katherine Kong, Martin Moorhead, Li Weng, Jianbiao Zheng, Malek Faham

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.0field-weighted citation impact, top 13% 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

26 citing papers in PubMed, 38 citations in OpenAlex.

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  20. T-cell receptor profiling in cancer.Molecular oncology · 2015
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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

6 authors.

Mark KlingerResearch, Sequenta Inc., South San Francisco, California, United States of America.
Katherine Kong
Martin Moorhead
Li Weng
Jianbiao Zheng
Malek Faham

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In this study, we combined a novel sequencing method, which can identify individual clonotypes based on their unique T cell receptor (TCR) rearrangement, with existing immune assays to characterize antigen-specific T cell responses. We validated this approach using three types of assays routinely used to measure antigen-specific responses: pentamers which enable identification of T cells bearing specific TCRs, activation marker expression following antigen stimulation and antigen-induced proliferation to identify cytomegalovirus (CMV) specific clonotypes. In one individual, 8 clonotypes were identified using a pentamer reagent derived from the CMV pp65 protein. The same 8 clonotypes were also identified following sequencing of cells that upregulated an activation marker following incubation with an identical peptide derived from pp65. These 8 and an additional 8 clonotypes were identified using a more sensitive CFSE-based proliferation assay. We found clear sequence homology among some of the clonotypes identified, and the CDR3 region in one clonotype was identical to a previously published pp65-specific clonotype sequence. Many of these CMV-specific clonotypes were present at frequencies below 10(-5) which are undetectable using standard flow-cytometric methods. These studies suggest that an immune response is comprised of a diverse set of clones, many of which are present at very low frequencies. Thus, the combination of immune assays and sequencing depicts the richness and diversity of an immune response at a level that is not possible using standard immune assays alone. The methods articulated in this work provide an enhanced understanding of T cell-mediated immune responses at the clonal level.

Indexed as

Amino Acid SequenceAntigensAntigens, ViralCD8-Positive T-LymphocytesComplementarity Determining RegionsCytomegalovirusEpitopes, T-LymphocyteFlow CytometryHigh-Throughput Nucleotide SequencingHumansImmunoassayImmunophenotypingLymphocyte ActivationPhosphoproteinsReceptors, Antigen, T-CellReceptors, Antigen, T-Cell, alpha-betaAntigensAntigens, ViralComplementarity Determining Regionscytomegalovirus matrix protein 65kDaEpitopes, T-LymphocytePhosphoproteinsReceptors, Antigen, T-CellReceptors, Antigen, T-Cell, alpha-betaTumor Necrosis Factor Receptor Superfamily, Member 9Viral Matrix Proteins

Identifiers

PMID24069285
PMCPMC3778005
OpenAlexW2043496713

What OpenQuestion holds

Textmetadata
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.