Structural basis of peptide binding and presentation by the type I diabetes-associated MHC class II molecule of NOD mice

Immunity. 2000 Jun;12(6):699-710. doi: 10.1016/s1074-7613(00)80220-4.


We have determined the crystal structure of I-Ag7, an integral component in murine type I diabetes development. Several features distinguish I-Ag7 from other non-autoimmune-associated MHC class II molecules, including novel peptide and heterodimer pairing interactions. The binding groove of I-Ag7 is unusual at both terminal ends, with a potentially solvent-exposed channel at the base of the P1 pocket and a widened entrance to the P9 pocket. Peptide binding studies with variants of the hen egg lysozyme I-Ag7 epitope HEL(11-25) support a comprehensive structure-based I-Ag7 binding motif. Residues critical for T cell recognition were investigated with a panel of HEL(11-25)-restricted clones, which uncovered P1 anchor-dependent structural variations. These results establish a framework for future experiments directed at understanding the role of I-Ag7 in autoimmunity.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Amino Acid Substitution / immunology
  • Animals
  • Antigen Presentation*
  • Chickens
  • Crystallography, X-Ray
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / metabolism
  • Dimerization
  • Epitope Mapping
  • Epitopes, T-Lymphocyte / metabolism
  • Histocompatibility Antigens Class II / chemistry*
  • Histocompatibility Antigens Class II / immunology
  • Histocompatibility Antigens Class II / metabolism*
  • Mice
  • Mice, Inbred NOD
  • Models, Molecular
  • Molecular Sequence Data
  • Muramidase / immunology
  • Muramidase / metabolism
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Peptides / chemistry*
  • Peptides / immunology*
  • Peptides / metabolism
  • Protein Binding / immunology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism


  • Epitopes, T-Lymphocyte
  • Histocompatibility Antigens Class II
  • Peptide Fragments
  • Peptides
  • Muramidase

Associated data

  • PDB/1F3J