Epitopes described in "Crystal structure of HLA-G: a nonclassical MHC class I molecule expressed at the fetal-maternal interface."

Article Authors:Craig S Clements; Lars Kjer-Nielsen; Lyudmila Kostenko; Hilary L Hoare; Michelle A Dunstone; Eric Moses; Katy Freed; Andrew G Brooks; Jamie Rossjohn; James McCluskey
Article Title:Crystal structure of HLA-G: a nonclassical MHC class I molecule expressed at the fetal-maternal interface.
Reference Detail
Reference ID:735
Abstract:HLA-G is a nonclassical major histocompatibility complex class I (MHC-I) molecule that is primarily expressed at the fetal-maternal interface, where it is thought to play a role in protecting the fetus from the maternal immune response. HLA-G binds a limited repertoire of peptides and interacts with the inhibitory leukocyte Ig-like receptors LIR-1 and LIR-2 and possibly with certain natural killer cell receptors. To gain further insights into HLA-G function, we determined the 1.9-A structure of a monomeric HLA-G complexed to a natural endogenous peptide ligand from histone H2A (RIIPRHLQL). An extensive network of contacts between the peptide and the antigen-binding cleft reveal a constrained mode of binding reminiscent of the nonclassical HLA-E molecule, thereby providing a structural basis for the limited peptide repertoire of HLA-G. The alpha3 domain of HLA-G, a candidate binding site for the LIR-1 and -2 inhibitory receptors, is structurally distinct from the alpha3 domains of classical MHC-I molecules, providing a rationale for the observed affinity differences for these ligands. The structural data suggest a head-to-tail mode of dimerization, mediated by an intermolecular disulfide bond, that is consistent with the observation of HLA-G dimers on the cell surface.
Affiliations:Protein Crystallography Unit, Monash Centre for Synchrotron Science, Department of Biochemistry and Molecular Biology, School of Biomedical Sciences, Monash University, Clayton, Victoria 3800, Australia.
Reference Type:Literature
PubMed ID:15718280
Journal:Proc Natl Acad Sci U S A
Journal Volume:102
Article Pages:3360-5
Journal ISSN:0027-8424
Article Chemical List:HLA Antigens;HLA-G Antigens;Histocompatibility Antigens Class I
Article MeSH List:Amino Acid Sequence; Animals; Crystallography, X-Ray; Female; HLA Antigens(chemistry; immunology); HLA-G Antigens; Histocompatibility Antigens Class I(chemistry; immunology); Humans; Maternal-Fetal Exchange(immunology); Mice; Models, Molecular; Molecular Sequence Data; Pregnancy; Protein Conformation; Sequence Homology, Amino Acid
Curation Last Updated:2015-06-05 00:12:04