MHC class I molecules exploit the low G plus C content of pathogen genomes for enhanced presentation

被引:13
作者
Calis, Jorg J. A. [1 ]
Sanchez-Perez, Gabino F. [1 ]
Kesmir, Can [1 ]
机构
[1] Univ Utrecht, Utrecht, Netherlands
关键词
G plus C content; HLA alleles; MHC-I presentation; Self/nonself discrimination; T-CELL EPITOPES; HLA-B ALLELES; QUANTITATIVE PREDICTIONS; BINDING-AFFINITY; PEPTIDE; PROTEIN; PROTEASOME; EVOLUTION; NETMHCPAN; DATABASE;
D O I
10.1002/eji.201040339
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Distinguishing self from nonself and pathogenic from nonpathogenic is a fundamental challenge to the immune system but whether adaptive immune systems use pathogen-specific signatures to achieve this is largely unknown. By investigating the presentation of large sets of viruses and bacteria on MHC class I molecules, we analyze whether MHC-I molecules have a preference for pathogen-derived peptides. The fraction of potential MHC-I binders in different organisms can vary up to eight-fold. We find that this variation can be largely explained by G+C content differences of the organisms, which are reflected in amino acid frequencies. A. significant majority of HLA-A, but not HLA-B, molecules has a preference for peptides derived from organisms with a low G+C content. Interestingly, a low G+C content seems to be a universal signature for pathogenicity. Finally, we find the same preferences in chimpanzee and rhesus macaque MHC-I molecules. These results demonstrate that despite the fast evolution of MHC-I alleles and their extreme polymorphism and diversity in peptide-binding preferences, MHC-I molecules can acquire a preference to exploit pathogen-specific signatures.
引用
收藏
页码:2699 / 2709
页数:11
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