Crystal structure of I-Ak in complex with a dominant epitope of lysozyme

Immunity. 1998 Mar;8(3):305-17. doi: 10.1016/s1074-7613(00)80536-1.


We have determined the structure of murine MHC class II I-Ak in complex with a naturally processed peptide from hen egg lysozyme (HEL residues 50-62) at 1.9 A resolution. These results provide a structural basis for the I-Ak peptide-binding motif. Binding is established by the deep burial of five anchor side chains into specific pockets of the I-Ak binding groove, with a zen-like fit of an aspartic acid in the P1 pocket. We also show that in the I-Ak alpha chain, a bulge occurs in the first strand of the peptide-binding platform, an insertion probably common to all I-A and HLA-DQ alleles. The I-Ak beta chain has a deletion in the helical region adjacent to the P7 pocket and an insertion in the helical region neighboring the P1 pocket. As a result of these structural features, the extended HEL peptide dips low into the center of the I-Ak groove and reaches toward solvent at its C-terminal end.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigen Presentation
  • Binding Sites
  • Crystallography, X-Ray
  • HLA-DR1 Antigen
  • Histocompatibility Antigens Class II / chemistry*
  • Histocompatibility Antigens Class II / genetics
  • Hydrogen Bonding
  • Immunodominant Epitopes / chemistry*
  • Mice
  • Models, Immunological
  • Models, Molecular
  • Molecular Sequence Data
  • Muramidase / chemistry*
  • Peptide Fragments / chemistry*
  • Protein Conformation
  • Protein Structure, Secondary
  • Recombinant Proteins / chemistry
  • Sequence Homology, Amino Acid


  • HLA-DR1 Antigen
  • Histocompatibility Antigens Class II
  • I-Ak antigen
  • Immunodominant Epitopes
  • Peptide Fragments
  • Recombinant Proteins
  • hen egg lysozyme peptide (50-62)
  • Muramidase

Associated data

  • PDB/1IAK