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Related Experiment Videos

Subtle conformational changes induced in major histocompatibility complex class II molecules by binding peptides

A V Chervonsky1, R M Medzhitov, L K Denzin

  • 1Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06510, USA.

Proceedings of the National Academy of Sciences of the United States of America
|August 26, 1998
PubMed
Summary

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Peptides induce structural changes in major histocompatibility complex (MHC) class II molecules, altering how T cells recognize them. These peptide-driven structural variations are crucial for T cell selection and may influence autoimmunity.

Area of Science:

  • Immunology
  • Molecular Biology
  • Cell Biology

Background:

  • Major histocompatibility complex (MHC) class II molecules traffic through endocytic compartments during antigen presentation.
  • In these compartments, antigenic peptides replace invariant chain fragments, a process facilitated by the DM protein.
  • Structural changes in MHC class II molecules occur during this process, impacting their recognition by T cells.

Purpose of the Study:

  • To investigate the structural transitions of MHC class II molecules induced by peptide binding.
  • To determine how these peptide-dependent structural variations affect T cell recognition.
  • To explore the implications of these findings for T cell selection and autoimmunity.

Main Methods:

  • Utilized a specific monoclonal antibody (mAb), 25-9-17, to probe structural differences in I-Ab complexes.

Related Experiment Videos

  • Assessed mAb binding to I-Ab complexed with different peptides (Ealpha chain-derived vs. invariant chain fragment).
  • Evaluated the ability of the mAb to block T cell hybridoma activation by I-Ab-peptide complexes.

    • Main Results:

    • The mAb 25-9-17 showed differential binding, interacting with I-Ab complexed with invariant chain peptides but not with Ealpha chain-derived peptides.
    • This mAb blocked activation of some I-Ab-reactive T cell hybridomas but not others, indicating peptide-dependent conformations.
    • Alloreactive T cells also demonstrated the ability to distinguish between these peptide-dependent variants of MHC class II molecules.

    Conclusions:

    • Bound peptides induce subtle, yet significant, structural transitions in MHC class II molecules.
    • These structural variations influence T cell recognition, highlighting the specificity of T cell-MHC interactions.
    • Peptide-imposed structural changes in MHC class II molecules may play a critical role in T cell selection and the development of autoimmune diseases.