Theoretical Biology and Bioinformatics, Utrecht University, Utrecht, The Netherlands.
Eur J Immunol. 2010 Oct;40(10):2699-709. doi: 10.1002/eji.201040339.
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.
区分自身和非自身以及致病和非致病是免疫系统面临的基本挑战，但适应性免疫系统是否利用病原体特异性特征来实现这一点在很大程度上尚不清楚。通过研究 MHC Ⅰ类分子上大量病毒和细菌的呈递，我们分析了 MHC-I 分子是否对病原体衍生肽具有偏好性。不同生物体中潜在 MHC-I 结合物的比例差异可达 8 倍。我们发现，这种差异在很大程度上可以通过生物体的 G+C 含量差异来解释，这反映在氨基酸频率上。很大一部分 HLA-A，但不是 HLA-B，分子对来自 G+C 含量低的生物体的肽具有偏好性。有趣的是，低 G+C 含量似乎是致病性的普遍特征。最后，我们在黑猩猩和恒河猴 MHC-I 分子中也发现了相同的偏好。这些结果表明，尽管 MHC-I 等位基因的进化速度很快，其在肽结合偏好方面表现出极端的多态性和多样性，但 MHC-I 分子可以获得利用病原体特异性特征的偏好性。
