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Related Experiment Videos

Mhc-guided processing: binding of large antigen fragments.

Eli E Sercarz1, Emanual Maverakis

  • 1Torrey Pines Institute for Molecular Studies, San Diego, California 92121, USA. esercarz@tpims.org

Nature Reviews. Immunology
|September 17, 2003
PubMed
Summary

This study challenges the traditional view of antigen processing. We present evidence that MHC class II molecules bind and trim antigens while they are still partially folded, suggesting a different pathway for peptide presentation.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Biochemistry

Background:

  • The established model for Major Histocompatibility Complex (MHC) class II antigen presentation involves unfolding and enzymatic cleavage of proteins into peptides before loading.
  • An alternative model proposes that MHC class II molecules bind partially unfolded antigens and then trim them while bound.

Purpose of the Study:

  • To investigate the validity of the alternative model for antigen processing and presentation by MHC class II molecules.
  • To determine the proportion of peptide cargo associated with MHC class II that originates from partially intact, bound antigens.

Main Methods:

  • Analysis of elutable peptide cargo from MHC class II molecules.
  • Comparison of peptide characteristics with predictions from both established and alternative models.

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Main Results:

  • A significant portion of the peptides eluted from MHC class II molecules are consistent with originating from antigens that were bound and trimmed while partially unfolded.
  • This finding suggests that the alternative model contributes substantially to the repertoire of presented peptides.

Conclusions:

  • The traditional model of antigen processing by MHC class II may be incomplete.
  • Antigen binding and subsequent trimming while the antigen is still partially folded represents a significant pathway for generating peptide cargo for MHC class II presentation.