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Related Experiment Videos

Peptide-induced conformational changes in class I molecules. Direct detection by flow cytometry

E M Rohren1, D J McCormick, L R Pease

  • 1Department of Immunology, Mayo Foundation, Rochester, MN 55905.

Journal of Immunology (Baltimore, Md. : 1950)
|June 1, 1994
PubMed
Summary

T cell activation involves T cell receptor (TCR) interactions with peptide-MHC complexes. Altering buried peptide residues can change MHC conformation, impacting T cell responses through direct or indirect mechanisms.

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Area of Science:

  • Immunology
  • Structural Biology
  • Molecular Interactions

Background:

  • T cell activation relies on interactions between the T cell receptor (TCR), peptide, and MHC class I molecules.
  • Previous studies suggest peptide modifications can influence T cell responses, hinting at indirect effects within the peptide-MHC complex.

Purpose of the Study:

  • To investigate the conformational changes in mouse MHC class I molecule Kb when bound to ovalbumin peptide and its analogues.
  • To determine if alterations at peptide position 2 (P2) affect MHC conformation and subsequent T cell stimulation.

Main Methods:

  • Utilized monoclonal antibodies (mAbs) to probe the conformation of the alpha 1 and alpha 2 domains of the Kb molecule.
  • Analyzed crystallographic data of Kb bound to ovalbumin peptide and 19 analogues differing at P2.

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  • Correlated conformational changes with T cell stimulation data.

    • Main Results:

    • Substitution of peptide residue at P2, which is buried within the antigen-binding cleft, induced measurable conformational changes in the MHC class I molecule.
    • These conformational changes directly correlated with the ability of the peptide-MHC complex to stimulate T cells.
    • Side chains at P2 are not directly accessible to the TCR.

    Conclusions:

    • Peptide binding to MHC class I can induce indirect conformational effects on the MHC molecule.
    • T cell activation can occur through direct TCR-MHC or TCR-peptide interactions, as well as indirectly via TCR recognition of MHC conformational changes induced by the peptide.
    • This provides a new model for understanding the multifaceted nature of T cell activation by peptide-MHC complexes.