title: A structural basis for antigen presentation by the MHC class Ib molecule, Qa-1b.
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.
authors: Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
authors: Li
authors: L
authors: Zeng
authors: Lucy C
authors: LC
authors: Sullivan
authors: Julian P
authors: JP
authors: Vivian
authors: Nicholas G
authors: NG
authors: Walpole
authors: Christopher M
authors: CM
authors: Harpur
authors: Jamie
authors: J
authors: Rossjohn
authors: Craig S
authors: CS
authors: Clements
authors: Andrew G
authors: AG
authors: Brooks
mesh_terms: D000818:Animals; D017951:Antigen Presentation / Q000502:physiology*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D006801:Humans; D051379:Mice; D055654:NK Cell Lectin-Like Receptor Subfamily C / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D051920:NK Cell Lectin-Like Receptor Subfamily D / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D010455:Peptides / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D013045:Species Specificity; D040681:Structural Homology, Protein; D013329:Structure-Activity Relationship; D000097625:HLA-E Antigens
chemical_list: D015395:Histocompatibility Antigens Class I; D055654:NK Cell Lectin-Like Receptor Subfamily C; D051920:NK Cell Lectin-Like Receptor Subfamily D; D010455:Peptides; D000097625:HLA-E Antigens; C032907:Q surface antigens