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Peptide:MHC Tetramer-based Enrichment of Epitope-specific T cells
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Quantifiable predictive features define epitope-specific T cell receptor repertoires.

Pradyot Dash1, Andrew J Fiore-Gartland2, Tomer Hertz2,3

  • 1Department of Immunology, St Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.

Nature
|June 22, 2017
PubMed
Summary
This summary is machine-generated.

T cell receptors (TCRs) recognizing the same epitope share conserved sequences, enabling predictive modeling of T cell specificity. This study characterized TCR repertoires, revealing clustered receptors with shared motifs crucial for adaptive immune recognition.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Bioinformatics

Background:

  • T cells use T cell receptors (TCRs) to recognize pathogen epitopes bound to peptide-MHC complexes.
  • TCR diversity is generated by V(D)J recombination, creating a vast potential repertoire.
  • Despite high diversity, TCRs recognizing the same epitope often exhibit conserved features.

Purpose of the Study:

  • To characterize epitope-specific T cell receptor repertoires in CD8+ T cells.
  • To develop analytical tools for TCR repertoire analysis and specificity prediction.
  • To identify conserved sequence features within epitope-specific TCR repertoires.

Main Methods:

  • Analysis of over 4,600 paired TCRαβ sequences from ten epitope-specific repertoires (mice and humans).
  • Development of a TCR distance metric for clustering and visualization.
  • Creation of a repertoire diversity metric and a distance-based classifier for TCR assignment.
  • Identification of shared sequence motifs and conserved residues.

Main Results:

  • Epitope-specific repertoires comprise clustered receptors with shared sequence similarities and diverse outlier sequences.
  • A distance-based classifier accurately assigns novel TCRs to characterized repertoires.
  • Key conserved residues driving TCR recognition were identified through motif analysis.

Conclusions:

  • Predictive modeling of TCR epitope specificity is feasible due to conserved sequence features.
  • Characterized TCR repertoires reveal underlying generalizable patterns of adaptive immune recognition.
  • The developed analytical tools facilitate the study of TCR repertoire structure and function.