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Although divergent in residues of the peptide binding site, conserved chimpanzee Patr-AL and polymorphic human HLA-A*02 have overlapping peptide-binding repertoires.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2011 Feb 01; Vol. 186 (3), pp. 1575-88. Date of Electronic Publication: 2011 Jan 05. - Publication Year :
- 2011
-
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 α(1) and α(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 α(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.
- Subjects :
- Animals
Binding Sites genetics
Binding Sites immunology
Cloning, Molecular
Conserved Sequence genetics
HLA-A Antigens chemistry
HLA-A Antigens genetics
HLA-A2 Antigen
Histocompatibility Antigens Class I chemistry
Histocompatibility Antigens Class I genetics
Humans
Molecular Sequence Data
Pan troglodytes
Peptides chemistry
Peptides genetics
Protein Binding genetics
Protein Binding immunology
Receptors, Antigen, T-Cell metabolism
Conserved Sequence immunology
Genes, Overlapping immunology
HLA-A Antigens metabolism
Histocompatibility Antigens Class I metabolism
Peptides metabolism
Polymorphism, Genetic
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 186
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 21209280
- Full Text :
- https://doi.org/10.4049/jimmunol.1002990