miHA-Match: Computational detection of tissue-specific minor histocompatibility antigens
miHA-Match: Computational detection of tissue-specific minor histocompatibility antigens
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DOI：
10.1016/j.jim.2012.09.004
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发表时间：
2012-12-14
影响因子：
2.2
通讯作者：
Kohlbacher, Oliver
中科院分区：
文献类型：
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作者：
Feldhahn, Magdalena;Doennes, Pierre;Kohlbacher, Oliver
异基因干细胞移植在许多血液恶性肿瘤，特别是白血病中显示出相当大的成功。有益的效果是由供体T细胞识别患者特异性HLA结合肽介导的。这些肽被称为次要组织相容性抗原（miHA），通常由单核苷酸多态性引起。组织特异性miHA已成功用于抗肿瘤治疗，而不会引起非特异性移植物抗宿主反应。然而，迄今为止，只有少量的miHA被确定，限制了临床使用。在这里，我们提出了一个免疫信息学管道识别miHA。该管道可用于大规模miHA筛查，例如诊断测试的开发。另一个有趣的应用是基于该管道检测到的患者-供体对特异性miHA设计基于miHA的个性化癌症疗法。建议的方法涵盖了遗传变异检测，替代转录的影响，和HLA-肽结合的各个方面。我们的计算流水线和实验得出的数据集的比较显示出计算预测的miHA的良好的一致性和覆盖率。(C)2012爱思唯尔有限公司版权所有。
Allogenic stem cell transplantation has shown considerable success in a number of hematological malignancies, in particular in leukemia. The beneficial effect is mediated by donor T cells recognizing patient-specific HLA-binding peptides. These peptides are called minor histocompatibility antigens (miHAs) and are typically caused by single nucleotide polymorphisms. Tissue-specific miHAs have successfully been used in anti-tumor therapy without causing unspecific graft-versus-host reactions. However, only a small number of miHAs have been identified to date, limiting the clinical use. Here we present an immunoinformatics pipeline for the identification of miHAs. The pipeline can be applied to large-scale miHA screening, for example, in the development of diagnostic tests. Another interesting application is the design of personalized miHA-based cancer therapies based on patient-donor pair-specific miHAs detected by this pipeline. The suggested method covers various aspects of genetic variant detection, effects of alternative transcripts, and HLA-peptide binding. A comparison of our computational pipeline and experimentally derived datasets shows excellent agreement and coverage of the computationally predicted miHAs. (C) 2012 Elsevier B.V. All rights reserved.