MHC class II function preserved by low-affinity peptide interactions preceding stable binding

Nature. 1994 Aug 25;370(6491):647-50. doi: 10.1038/370647a0.


Major histocompatibility complex class II molecules and their peptide ligands show unusual interaction kinetics, with slow association and dissociation rates that yield an apparent equilibrium constant of approximately 10(-6)-10(-8) M (refs 1-5). However, there is evidence for a specific, rapidly formed, short-lived complex. The altered migration on SDS-polyacrylamide gel electrophoresis of class II molecules upon stable peptide binding has led to the hypothesis that the two kinetically distinguishable types of class II-peptide complexes correspond to different structures. In accord with this model, we demonstrate here that insect cell-derived HLA-DR1 class II molecules show fast, almost stoichiometric occupancy with rapidly dissociating peptide while remaining sensitive to SDS-induced chain dissociation. The same DR1 molecules slowly and quantitatively form long-lived complexes resistant to SDS-induced denaturation. Surprisingly, low-affinity interaction with peptide protects class II from denaturation at physiological temperature, a finding that has implications for understanding the role of invariant chain in the intracellular behaviour of class II molecules.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Chromatography, High Pressure Liquid
  • Electrophoresis, Polyacrylamide Gel
  • HLA-DR1 Antigen / chemistry
  • HLA-DR1 Antigen / metabolism*
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins, Viral / metabolism*
  • Kinetics
  • Molecular Sequence Data
  • Moths
  • Peptide Fragments / metabolism*
  • Protease Inhibitors / pharmacology
  • Protein Binding


  • HLA-DR1 Antigen
  • Hemagglutinin Glycoproteins, Influenza Virus
  • Hemagglutinins, Viral
  • Peptide Fragments
  • Protease Inhibitors
  • influenza hemagglutinin (306-318)