Individual hydrogen bonds play a critical role in MHC class II:peptide interactions: Implications for the dynamic aspects of class II trafficking and DM-mediated peptide exchange

Andrea J. Sant, Craig Beeson, Benjamin McFarland, Jun Cao, Stephanie Ceman, Paula Wolf Bryant, Shenhong Wu

Research output: Contribution to journalArticlepeer-review

Abstract

Determination of the crystal structure of class II:peptide complexes has shown that in addition to pocket interactions involving the side chains of the peptide, peptide binding to MHC class II molecules is characterized by a series of hydrogen bonds which are contributed by genetically conserved amino acid residues in the class II molecule to the main chain of the peptide. Our experiments have revealed an unexpectedly large contribution of hydrogen bonds at the periphery of the MHC peptide binding pocket to MHC class II function. Kinetic studies have shown that peptide dissociation rates are profoundly accelerated by loss of a single hydrogen bonding residue. The magnitude of the effects seen with the loss in potential for a single hydrogen bond support a co-operative model in which individual bonds between class II and peptide are dependent on the integrity of neighboring interactions. Collectively our studies have revealed that MHC class II structure, peptide binding and intracellular trafficking events are critically dependent on the integrity of the hydrogen bonding network between class II molecules and its bound peptide.

Original languageEnglish (US)
Pages (from-to)239-253
Number of pages15
JournalImmunological Reviews
Volume172
DOIs
StatePublished - Jan 1 1999
Externally publishedYes

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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