Human self-protein CD8+ T-cell epitopes are both positively and negatively selected.

Human self-protein CD8+ T-cell epitopes are both positively and negatively selected.
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DOI:
10.1002/eji.200838353
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发表时间:
2009-04
影响因子:
5.4
通讯作者:
Louzoun Y
Louzoun Y
中科院分区:
医学3区
文献类型:
--
作者:
Almani M;Raffaeli S;Vider-Shalit T;Tsaban L;Fishbain V;Louzoun Y

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细胞免疫系统在MHC-I分子的背景下识别自身表位。免疫学的一般观点认为,这些自身表位只是一个背景,积极和消极地选择T细胞。我们在这里估计了许多常见的HLA等位基因在每个人类蛋白质中的表位的数量,以及代表这些蛋白质上的表位的过度或不足呈递的分数。我们进一步表明,有一个明确的选择特定的自我蛋白类型的介绍。呈递许多表位的蛋白包括例如AIRE上调的组织特异性抗原、免疫系统受体和具有高表达水平的蛋白。另一方面,可能被认为对免疫系统不太“有用”的蛋白质,如低表达水平蛋白质,被低估。我们联合收割机将我们的表位估计与SNP测量相结合,以表明这种选择可以通过非同义SNP的分数(替换分数)直接观察到,该分数在表位内部显著高于外部
The cellular immune system recognizes self epitopes in the context of MHC-I molecules. The immunological general view presumes that these self epitopes are just a background, both positively and negatively selecting T cells. We here estimate the number of epitopes in each human protein for many frequent HLA alleles, and a score representing over or under presentation of epitopes on these proteins. We further show that there is a clear selection for the presentation of specific self proteins types. Proteins presenting many epitopes include for example AIRE upregulated Tissue specific antigens, immune system receptors and proteins with a high expression level. On the other hand, proteins that may be considered less “useful” for the immune system, such as low expression level proteins, are under presented. We combine our epitope estimate with SNP measures to show that this selection can be directly observed through the fraction of non-synonymous SNPs (replacement fraction), which is significantly higher inside epitopes than outside
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