A structural basis for antigen presentation by the MHC class Ib molecule, Qa-1b

J Immunol. 2012 Jan 1;188(1):302-10. doi: 10.4049/jimmunol.1102379. Epub 2011 Nov 30.

Abstract

The primary function of the monomorphic MHC class Ib molecule Qa-1(b) is to present peptides derived from the leader sequences of other MHC class I molecules for recognition by the CD94-NKG2 receptors expressed by NK and T cells. Whereas the mode of peptide presentation by its ortholog HLA-E, and subsequent recognition by CD94-NKG2A, is known, the molecular basis of Qa-1(b) function is unclear. We have assessed the interaction between Qa-1(b) and CD94-NKG2A and shown that they interact with an affinity of 17 μM. Furthermore, we have determined the structure of Qa-1(b) bound to the leader sequence peptide, Qdm (AMAPRTLLL), to a resolution of 1.9 Å and compared it with that of HLA-E. The crystal structure provided a basis for understanding the restricted peptide repertoire of Qa-1(b). Whereas the Qa-1(b-AMAPRTLLL) complex was similar to that of HLA-E, significant sequence and structural differences were observed between the respective Ag-binding clefts. However, the conformation of the Qdm peptide bound by Qa-1(b) was very similar to that of peptide bound to HLA-E. Although a number of conserved innate receptors can recognize heterologous ligands from other species, the structural differences between Qa-1(b) and HLA-E manifested in CD94-NKG2A ligand recognition being species specific despite similarities in peptide sequence and conformation. Collectively, our data illustrate the structural homology between Qa-1(b) and HLA-E and provide a structural basis for understanding peptide repertoire selection and the specificity of the interaction of Qa-1(b) with CD94-NKG2 receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigen Presentation / physiology*
  • Binding Sites
  • Crystallography, X-Ray
  • Histocompatibility Antigens Class I / chemistry*
  • Histocompatibility Antigens Class I / genetics
  • Histocompatibility Antigens Class I / immunology
  • Humans
  • Mice
  • NK Cell Lectin-Like Receptor Subfamily C / chemistry*
  • NK Cell Lectin-Like Receptor Subfamily C / genetics
  • NK Cell Lectin-Like Receptor Subfamily C / immunology
  • NK Cell Lectin-Like Receptor Subfamily D / chemistry*
  • NK Cell Lectin-Like Receptor Subfamily D / genetics
  • NK Cell Lectin-Like Receptor Subfamily D / immunology
  • Peptides / chemistry*
  • Peptides / genetics
  • Peptides / immunology
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Species Specificity
  • Structural Homology, Protein
  • Structure-Activity Relationship

Substances

  • HLA-E antigen
  • Histocompatibility Antigens Class I
  • NK Cell Lectin-Like Receptor Subfamily C
  • NK Cell Lectin-Like Receptor Subfamily D
  • Peptides
  • Q surface antigens