Evidence map›Paper›PMID 25376839›Full record

ArticleNature communications2014

Changing the peptide specificity of a human T-cell receptor by directed evolution.

Sheena N Smith, Yuhang Wang, Javier L Baylon, Nishant K Singh, Brian M Baker, Emad Tajkhorshid, David M Kranz

Open access · bronzeAbstract read
In one paragraph

Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

22 citing papers in PubMed, 30 citations in OpenAlex.

  1. Review
  2. T-cell receptors that areFrontiers in immunology · 2025
    Article
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. T-cell Receptors EngineeredCancer immunology research · 2019
    Article
  14. Probing pathways of adaptation with continuous evolution.Current opinion in systems biology · 2019
    Article
  15. Review
  16. Review
  17. Article
  18. Review
  19. Review
  20. Article
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 1 country.

Sheena N SmithDepartment of Biochemistry, University of Illinois, 600 South Matthews Avenue, Urbana, Illinois 61801, USA.
Yuhang WangCenter for Biophysics and Computational Biology, University of Illinois, Urbana, Illinois 61802, USA.
Javier L BaylonCenter for Biophysics and Computational Biology, University of Illinois, Urbana, Illinois 61802, USA.
Nishant K SinghDepartment of Chemistry and Biochemistry and the Harper Cancer Research Institute, University of Notre Dame, 1234 Notre Dame Avenue, South Bend, Indiana 46557, USA.
Brian M BakerDepartment of Chemistry and Biochemistry and the Harper Cancer Research Institute, University of Notre Dame, 1234 Notre Dame Avenue, South Bend, Indiana 46557, USA.
Emad Tajkhorshid1] Department of Biochemistry, University of Illinois, 600 South Matthews Avenue, Urbana, Illinois 61801, USA [2] Center for Biophysics and Computational Biology, University of Illinois, Urbana, Illinois 61802, USA.
David M KranzDepartment of Biochemistry, University of Illinois, 600 South Matthews Avenue, Urbana, Illinois 61801, USA.
University of Illinois Urbana-Champaign · USUniversity of Notre Dame · US

Funding

Synthetic Antigen Binder CoreU54GM087519 · NIGMS · UNIVERSITY OF CHICAGO · PI NAKAMOTO, ROBERT K. · 2010 to 2017
$31.9M
WHOLE CELL SIMULATIONP41GM104601 · NIGMS · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI TAJKHORSHID, EMAD · 2012 to 2021
$19.0M
Training Program in Chemistry-Interface with BiologyT32GM070421 · NIGMS · UNIVERSITY OF ILLINOIS URBANA-CHAMPAIGN · PI HERGENROTHER, PAUL · 2005 to 2019
$5.4M
Physical Basis for T Cell Receptor Binding and ActivityR01GM067079 · NIGMS · UNIVERSITY OF NOTRE DAME · PI BAKER, BRIAN M · 2003 to 2015
$3.5M
Engineering T Cell Receptors for Adoptive Cell TherapiesR01CA178844 · NCI · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · PI KRANZ, DAVID M. · 2014 to 2018
$1.6M
Development of a Computational Framework for TCR EngineeringR01GM103773 · NIGMS · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI BAKER, BRIAN M, WENG, ZHIPING · 2013 to 2016
$1.2M
NCI NIH HHS R01 CA178844NIGMS NIH HHS GM067079NIGMS NIH HHS GM103773NIGMS NIH HHS P41 GM104601NIGMS NIH HHS P41-GM104601NIGMS NIH HHS R01 GM067079NIGMS NIH HHS R01 GM103773NIGMS NIH HHS T32 GM070421NIGMS NIH HHS U54 GM087519NIGMS NIH HHS U54-GM087519
6 · The paper itself

Abstract

Binding of a T-cell receptor (TCR) to a peptide/major histocompatibility complex is the key interaction involved in antigen specificity of T cells. The recognition involves up to six complementarity determining regions (CDR) of the TCR. Efforts to examine the structural basis of these interactions and to exploit them in adoptive T-cell therapies has required the isolation of specific T-cell clones and their clonotypic TCRs. Here we describe a strategy using in vitro-directed evolution of a single TCR to change its peptide specificity, thereby avoiding the need to isolate T-cell clones. The human TCR A6, which recognizes the viral peptide Tax/HLA-A2, was converted to TCR variants that recognized the cancer peptide MART1/HLA-A2. Mutational studies and molecular dynamics simulations identified CDR residues that were predicted to be important in the specificity switch. Thus, in vitro engineering strategies alone can be used to discover TCRs with desired specificities.

Indexed as

Evolution, MolecularAmino Acid SequenceClone CellsComplementarity Determining RegionsEpitopesHLA-A2 AntigenHumansIn Vitro TechniquesMajor Histocompatibility ComplexMART-1 AntigenModels, MolecularMolecular Sequence DataMutationOligopeptidesProtein BindingProtein ConformationComplementarity Determining RegionsEpitopesHLA-A2 Antigenleucyl-leucyl-phenylalanyl-glycyl-tyrosyl-prolyl-valyl-tyrosyl-valineMART-1 AntigenOligopeptidesReceptors, Antigen, T-Cell

Identifiers

PMID25376839
PMCPMC4225554
OpenAlexW1983063722

What OpenQuestion holds

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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.