Evidence map›Paper›PMID 17975674›Full record

ArticleThe Journal of clinical investigation2007

Portable flanking sequences modulate CTL epitope processing.

Sylvie Le Gall, Pamela Stamegna, Bruce D Walker

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of clinical investigation, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
3.0field-weighted citation impact, top 8% 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

65 citing papers in PubMed, 98 citations in OpenAlex.

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  9. Therapeutic Vaccines for the Treatment of HIV.Translational research : the journal of laboratory and clinical medicine · 2020
    Review
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5 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors at 2 institutions in 1 country.

Sylvie Le GallPartners AIDS Research Center and Howard Hughes Medical Institute, Massachusetts General Hospital (MGH), Harvard Medical School, Boston, Massachusetts 02129, USA. sylvie_legall@hms.harvard.edu
Pamela Stamegna
Bruce D Walker
Howard Hughes Medical Institute · USAllergy Associates Research Center · US

Funding

The impact of HIV viral diversity and cellular immunity on HIV pathogenesisP30AI060354 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI ROBERT A. PARKER · 2004 to 2026
$94.4M
HIV-1-SPECIFIC T CELL CLONESR01AI028568 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI WALKER, BRUCE D · 1989 to 2008
$1.9M
HIV-1 SPECIFIC T CELL CLONESR37AI028568 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI WALKER, BRUCE D · 1994 to 2003
$1.6M
Role of antigen processing HIV CTL immunodominanceR21AI060502 · NIAID · MASSACHUSETTS GENERAL HOSPITAL · PI LE GALL, SYLVIE · 2004 to 2005
$519k
NIAID NIH HHS AI 060354NIAID NIH HHS AI060502-01A1NIAID NIH HHS AI28568-16NIAID NIH HHS P30 AI060354NIAID NIH HHS R01 AI028568NIAID NIH HHS R21 AI060502NIAID NIH HHS R37 AI028568
6 · The paper itself

Abstract

Peptide presentation is critical for immune recognition of pathogen-infected cells by CD8+ T lymphocytes. Although a limited number of immunodominant peptide epitopes are consistently observed in diseases such as HIV-1 infection, the relationship between immunodominance and antigen processing in humans is largely unknown. Here, we have demonstrated that endogenous processing and presentation of a human immunodominant HIV-1 epitope is more efficient than that of a subdominant epitope. Furthermore, we have shown that the regions flanking the immunodominant epitope constitute a portable motif that increases the production and antigenicity of otherwise subdominant epitopes. We used a novel in vitro degradation assay involving cytosolic extracts as well as endogenous intracellular processing assays to examine 2 well-characterized HIV-1 Gag overlapping epitopes presented by the same HLA class I allele, one of which is consistently immunodominant and the other subdominant in infected persons. The kinetics and products of degradation of HIV-1 Gag favored the production of peptides encompassing the immunodominant epitope and destruction of the subdominant one. Notably, cytosolic digestion experiments revealed flanking residues proximal to the immunodominant epitope that increased the production and antigenicity of otherwise subdominant epitopes. Furthermore, specific point mutations in these portable flanking sequences modulated the production and antigenicity of epitopes. Such portable epitope processing determinants provide what we believe is a novel approach to optimizing CTL responses elicited by vaccine vectors.

Indexed as

Base SequenceAmino Acid SequenceAnimalsAntigen PresentationCD8-Positive T-LymphocytesGene Products, gagHeLa CellsHIV-1HIV AntigensHIV InfectionsHLA-A3 AntigenHumansImmunodominant EpitopesMiceMolecular Sequence DataPoint MutationGene Products, gagHIV AntigensHLA-A3 AntigenImmunodominant Epitopes

Identifiers

PMID17975674
PMCPMC2045603
OpenAlexW2039456204

What OpenQuestion holds

Textmetadata
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.