Epitopes described in "Although divergent in residues of the peptide binding site, conserved chimpanzee Patr-AL and polymorphic human HLA-A*02 have overlapping peptide-binding repertoires."

Article Authors:Michael Gleimer; Angela R Wahl; Heather D Hickman; Laurent Abi-Rached; Paul J Norman; Lisbeth A Guethlein; John A Hammond; Monia Draghi; Erin J Adams; Sean Juo; Roxana Jalili; Baback Gharizadeh; Mostafa Ronaghi; K Christopher Garcia; William H Hildebrand; Peter Parham
Article Title:Although divergent in residues of the peptide binding site, conserved chimpanzee Patr-AL and polymorphic human HLA-A*02 have overlapping peptide-binding repertoires.
Reference Detail
Reference ID:1021478
Abstract:Patr-AL is an expressed, non-polymorphic MHC class I gene carried by ∼50% of chimpanzee MHC haplotypes. Comparing Patr-AL(+) and Patr-AL(-) haplotypes showed Patr-AL defines a unique 125-kb genomic block flanked by blocks containing classical Patr-A and pseudogene Patr-H. Orthologous to Patr-AL are polymorphic orangutan Popy-A and the 5' part of human pseudogene HLA-Y, carried by ∼10% of HLA haplotypes. Thus, the AL gene alternatively evolved in these closely related species to become classical, nonclassical, and nonfunctional. Although differing by 30 aa substitutions in the peptide-binding (1) and (2) domains, Patr-AL and HLA-A*0201 bind overlapping repertoires of peptides; the overlap being comparable with that between the A*0201 and A*0207 subtypes differing by one substitution. Patr-AL thus has the A02 supertypic peptide-binding specificity. Patr-AL and HLA-A*0201 have similar three-dimensional structures, binding peptides in similar conformation. Although comparable in size and shape, the B and F specificity pockets of Patr-AL and HLA-A*0201 differ in both their constituent residues and contacts with peptide anchors. Uniquely shared by Patr-AL, HLA-A*0201, and other members of the A02 supertype are the absence of serine at position 9 in the B pocket and the presence of tyrosine at position 116 in the F pocket. Distinguishing Patr-AL from HLA-A*02 is an unusually electropositive upper face on the (2) helix. Stimulating PBMCs from Patr-AL(-) chimpanzees with B cells expressing Patr-AL produced potent alloreactive CD8 T cells with specificity for Patr-AL and no cross-reactivity toward other MHC class I molecules, including HLA-A*02. In contrast, PBMCs from Patr-AL(+) chimpanzees are tolerant of Patr-AL.
Reference Type:Literature
PubMed ID:21209280
Journal:J Immunol
Journal Volume:186
Article Pages:1575-88
Journal ISSN:0022-1767
Article Chemical List:HLA-A Antigens;HLA-A*02 antigen;HLA-A2 Antigen;Histocompatibility Antigens Class I;Peptides;Receptors, Antigen, T-Cell
Article MeSH List:Animals; Binding Sites(genetics; immunology); Cloning, Molecular; Conserved Sequence(genetics; immunology); Genes, Overlapping(immunology); HLA-A Antigens(chemistry; genetics; metabolism); HLA-A2 Antigen; Histocompatibility Antigens Class I(chemistry; genetics; metabolism); Humans; Molecular Sequence Data; Pan troglodytes; Peptides(chemistry; genetics; metabolism); Polymorphism, Genetic; Protein Binding(genetics; immunology); Receptors, Antigen, T-Cell(metabolism)
Curation Last Updated:2016-04-05 22:57:17