The effect of anchor residue modifications on the stability of major histocompatibility complex class I-peptide interactions

Eur J Immunol. 1993 Apr;23(4):840-5. doi: 10.1002/eji.1830230411.


Anchor residues in peptides determine the specificity of binding to major histocompatibility complex class I molecules through interactions of their side chains with pockets in the peptide-binding groove. We have compared the kinetics of association of a Sendai virus nucleoprotein-derived peptide (FAPGNYPAL, termed SV9) with H-2Kb class I molecules, and the same peptide iodinated on the anchor residue tyrosine (125I-SV9). Even though the association rates were too rapid for direct measurements, competition studies indicated that they were similar for SV9 and 125I-SV9. To measure the binding of non-radioactive SV9 directly, SV9 was tritiated (3H-SV9). 3H-SV9 remained stably associated with H-2Kb molecules, whereas 125I-SV9 dissociated in a temperature-dependent fashion. Thus, modifications on anchor residues do not necessarily have to affect the specificity and association kinetics of peptide binding to class I molecules but can affect the stability of the resulting class I-peptide interaction. The dissociation of peptides with modified and, more generally, suboptimal anchor residue side chains may explain the presence of empty class I molecules and free class I heavy chains at the cell surface.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antigens, Viral / chemistry*
  • H-2 Antigens / metabolism*
  • Molecular Sequence Data
  • Monoiodotyrosine / chemistry
  • Nucleocapsid Proteins
  • Nucleoproteins*
  • Parainfluenza Virus 1, Human / immunology
  • Peptides / chemistry
  • Peptides / immunology*
  • Protein Binding
  • Structure-Activity Relationship
  • Temperature
  • Tyrosine / chemistry
  • Viral Core Proteins / chemistry
  • Viral Core Proteins / immunology*


  • Antigens, Viral
  • H-2 Antigens
  • Nucleocapsid Proteins
  • Nucleoproteins
  • Peptides
  • Viral Core Proteins
  • Tyrosine
  • Monoiodotyrosine