Structural features impose tight peptide binding specificity in the nonclassical MHC molecule HLA-E

Mol Cell. 1998 Mar;1(4):531-41. doi: 10.1016/s1097-2765(00)80053-2.


The crystal structure of the nonclassical human class lb MHC molecule HLA-E has been determined in complex with a prototypic ligand, the nonamer peptide (VMAPRTVLL), derived from the highly conserved residues 3-11 of the human MHC class la leader sequence. The mode of peptide binding retains some of the standard features observed in MHC class la complexes, but novel features imply that HLA-E has evolved to mediate specific binding to a tightly defined set of almost identical hydrophobic peptides from the highly conserved class l leader sequences. These molecular adaptations make HLA-E a rigorous checkpoint at the cell surface reporting on the integrity of the antigen processing pathway to CD94/NKG2 receptor-bearing natural killer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Crystallography
  • HLA Antigens / chemistry*
  • HLA Antigens / metabolism*
  • HLA-B8 Antigen / chemistry
  • Histocompatibility Antigens Class I / chemistry*
  • Histocompatibility Antigens Class I / metabolism*
  • Humans
  • Hydrogen Bonding
  • Peptide Fragments / chemistry
  • Protein Binding / immunology
  • Protein Conformation
  • Protein Structure, Secondary
  • Protein Structure, Tertiary


  • HLA Antigens
  • HLA-B8 Antigen
  • HLA-E antigen
  • Histocompatibility Antigens Class I
  • Peptide Fragments