Dipeptides catalyze rapid peptide exchange on MHC class I molecules

Proc Natl Acad Sci U S A. 2015 Jan 6;112(1):202-7. doi: 10.1073/pnas.1418690112. Epub 2014 Dec 22.


Peptide ligand selection by MHC class I molecules, which occurs by iterative optimization, is the centerpiece of immunodominance in antiviral and antitumor immune responses. For its understanding, the molecular mechanisms of peptide binding and dissociation by class I molecules must be elucidated. To this end, we have investigated dipeptides that bind to the F pocket of class I molecules. We find that they accelerate the dissociation of prebound peptides of both low and high affinity, suggesting a mechanism of action for the peptide-exchange chaperone tapasin. Peptide exchange on class I molecules also has practical uses in epitope discovery and T-cell monitoring.

Keywords: MHC tetramers; dipeptides; immunotherapy; peptide exchange; tapasin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Biocatalysis*
  • Dipeptides / metabolism*
  • Epitopes / immunology
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Molecular Sequence Data
  • Phenylalanine / analogs & derivatives
  • Phenylalanine / chemistry
  • Phenylalanine / metabolism
  • Protein Multimerization


  • Dipeptides
  • Epitopes
  • Histocompatibility Antigens Class I
  • cyclohexylalanine
  • Phenylalanine