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Updated: Feb 8, 2026

Measuring TCR-pMHC Binding In Situ using a FRET-based Microscopy Assay
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TCR-pMHC interactions: Two peptide repertoires-one signal.

M Cohn1

  • 1Conceptual Immunology Group, The Salk Institute, La Jolla, California.

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PubMed
Summary

The T-cell receptor (TCR) recognizes peptide fragments presented by the Major Histocompatibility Complex (MHC). This interaction involves distinct peptide segments, leading to independent recognition but cooperative function for immune specificity.

Keywords:
MHCPolyreactivityT cellTCRpeptide repertoiresprotein processingrestrictive recognition

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Area of Science:

  • Immunology
  • Molecular Biology
  • Structural Biology

Background:

  • T-cell receptors (TCRs) interact with peptide-MHC complexes.
  • This interaction is crucial for adaptive immunity.
  • Understanding TCR specificity is a key challenge in immunology.

Purpose of the Study:

  • To analyze the dual recognition of peptides by TCRs and MHC molecules.
  • To investigate the implications for TCR specificity and signaling.
  • To explore the role of differential peptide processing.

Main Methods:

  • Analysis of peptide-TCR interactions.
  • Examination of MHC peptide-binding sites.
  • Theoretical modeling of immune recognition.

Main Results:

  • Peptides are viewed differently by TCRs and MHC molecules, creating distinct recognition repertoires (Ptcr and Pr).
  • These repertoires are recognized independently yet function cooperatively.
  • Differential processing of peptides influences TCR recognition.

Conclusions:

  • The dual perspective of TCR and MHC on peptides shapes immune responses.
  • TCRs exhibit high polyreactivity from an immunologist's view but high specificity from the immune system's perspective.
  • This framework enhances understanding of TCR specificity, signaling, and immune system function.