Although Divergent in Residues of the Peptide Binding Site, Conserved Chimpanzee Patr-AL and Polymorphic Human HLA-A*02 Have Overlapping Peptide-Binding Repertoires

作者：Gleimer Michael; Wahl Angela R; Hickman Heather D; Abi Rached Laurent; Norman Paul J; Guethlein Li**eth A; Hammond John A; Draghi Monia; Adams Erin J; Juo Sean; Jalili Roxana; Gharizadeh Baback; Ronaghi Mostafa; Garcia K Christopher; Hildebrand William H; Parham Peter^*

来源：The Journal of Immunology, 2011, 186(3): 1575-1588.

DOI：10.4049/jimmunol.1002990

Patr-AL is an expressed, non-polymorphic MHC class I gene carried by similar to 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 similar to 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 alpha(1) and alpha(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 alpha(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. The Journal of Immunology, 2011, 186: 1575-1588.

• 出版日期2011-2-1