Evidence map›Paper›PMID 21992180›Full record

ArticleJournal of translational medicine2011

Heat shock protein 70/peptide complexes: potent mediators for the generation of antiviral T cells particularly with regard to low precursor frequencies.

Sabine Tischer, Megan Basila, Britta Maecker-Kolhoff, Stephan Immenschuh, Mathias Oelke, Rainer Blasczyk, Britta Eiz-Vesper

Open access · goldAbstract read
In one paragraph

Article in Journal of translational medicine, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

6 citing papers in PubMed, 16 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

7 authors at 2 institutions in 2 countries.

Sabine TischerInstitute for Transfusion Medicine, Hannover Medical School, Germany.
Megan Basila
Britta Maecker-Kolhoff
Stephan Immenschuh
Mathias Oelke
Rainer Blasczyk
Britta Eiz-Vesper
Medizinische Hochschule Hannover · DEJohns Hopkins Medicine · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHeat shock protein 70 (HSP70) has gained major attention as an adjuvant capable of inducing antigen-specific CD8(+) and CD4(+) T-cell responses. The ability of HSP70/peptide complexes to elicit cytotoxic T-cell (CTL) responses by cross-presentation of exogenous antigens via HLA class I molecules is of central interest in immunotherapy. We examined the role of HSP70/CMVpp65(495-503)-peptide complex (HSP70/CMV-PC) in HLA class I-restricted cross-presentation for ex vivo expansion of CMV-specific CTLs.

methodsCMV-specific T cells generated from PBMCs of HLA-A*02:01/CMV-seropositive donors were stimulated for 21 days with HSP70/CMV-PC and analyzed in functional assays. As a control PBMCs were cultured in the presence of CMVpp65(495-503) peptide or HSP70. Increase of CMV-specific CTLs was visualized by pentameric HLA-A*02:01/CMVpp65(495-503) complex.

resultsAbout 90% of HSP70/CMV-PC generated T cells were CMV-specific and exhibited significantly higher IFN-γ secretion, cytotoxic activity, and an increased heme oxygenase 1 (HO-1) gene expression as compared to about 69% of those stimulated with CMVpp65(495-503) peptide. We decided to classify the HLA-A*02:01/CMV-seropositive donors as weak, medium, and strong responder according to the frequency of generated A2/CMV-pentamer-positive CD8(+) T cells. HSP70/CMV-PC significantly induces strong antiviral T-cell responses especially in those donors with low memory precursor frequencies. Blockage of CD91 with α2-macroglobulin markedly reduced proliferation of antiviral T cells suggesting a major role of this receptor in the uptake of HSP70/CMV-PC.

conclusionThis study clearly demonstrates that HSP70/CMV-PC is a potent mediator to induce stronger T-cell responses compared to antiviral peptides. This simple and efficient technique may help to generate significant quantities of antiviral CTLs by cross-presentation. Thus, we propose HSP70 for chaperoning peptides to reach an efficient level of cross-presentation. HSP70/peptide complexes may be particularly useful to generate stronger T-cell responses in cases of low precursor frequencies and may help to improve the efficiency of antigen-specific T-cell therapy for minor antigens.

Indexed as

alpha-MacroglobulinsAntiviral AgentsCell ProliferationCytotoxicity, ImmunologicEnzyme-Linked Immunosorbent AssayFlow CytometryGene Expression Regulation, EnzymologicGranzymesHeme Oxygenase-1HSP70 Heat-Shock ProteinsHumansInterferon-gammaLymphocyte ActivationPeptidesPhosphoproteinsReverse Transcriptase Polymerase Chain Reactionalpha-MacroglobulinsAntiviral Agentscytomegalovirus matrix protein 65kDaGranzymesHeme Oxygenase-1HSP70 Heat-Shock ProteinsInterferon-gammaPeptidesPhosphoproteinsRNA, MessengerViral Matrix Proteins

Identifiers

PMID21992180
PMCPMC3217864
OpenAlexW2111014708

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.