NetMHCpan, a method for quantitative predictions of peptide binding to any HLA-A and -B locus protein of known sequence.
NetMHCpan, a method for quantitative predictions of peptide binding to any HLA-A and -B locus protein of known sequence.
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DOI：
10.1371/journal.pone.0000796
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发表时间：
2007-08-29
期刊：
影响因子：
3.7
通讯作者：
Buus S
中科院分区：
文献类型：
--
作者：
Nielsen M;Lundegaard C;Blicher T;Lamberth K;Harndahl M;Justesen S;Røder G;Peters B;Sette A;Lund O;Buus S
多肽与主要组织相容性复合体(MHC)分子的结合是细胞免疫系统识别病原体的唯一最具选择性的步骤。人类MHC-I类系统(HLA-I)具有极高的多态性。目前注册的人类白细胞抗原-I分子已超过1500个。单独确定每一种的特殊性将是一项重大的任务。在这里，我们利用已知的多肽-人类白细胞抗原-I相互作用的大型数据库来开发一种生物信息学方法，该方法同时考虑了多肽和人类白细胞抗原序列信息，并对任何多肽-人类白细胞抗原-I相互作用的亲和力进行定量预测。对预测将与先前未测试的HLA-I分子结合的多肽进行前瞻性实验验证，对已知的HIV免疫表位和内源性呈现多肽进行交叉验证和追溯预测，所有这些都成功地验证了该方法。我们进一步证明，该方法可以用于执行MHC特异性的聚类分析，并建议使用这种聚类来选择特别有信息的新MHC分子，用于未来的生化和功能分析。这种高通量的计算方法涵盖了所有的人类白细胞抗原分子，不仅适合于基因组和病原体范围的表位搜索，而且还适用于整个人类白细胞抗原的表位搜索。因此，它提供了真正的全球免疫反应分析，支持疫苗和免疫疗法的合理发展。它还有望为人类白细胞抗原结构-功能关系提供新的基本见解。该方法可在http://www.cbs.dtu.dk/services/NetMHCpan.上获得。
Binding of peptides to Major Histocompatibility Complex (MHC) molecules is the single most selective step in the recognition of pathogens by the cellular immune system. The human MHC class I system (HLA-I) is extremely polymorphic. The number of registered HLA-I molecules has now surpassed 1500. Characterizing the specificity of each separately would be a major undertaking. Here, we have drawn on a large database of known peptide-HLA-I interactions to develop a bioinformatics method, which takes both peptide and HLA sequence information into account, and generates quantitative predictions of the affinity of any peptide-HLA-I interaction. Prospective experimental validation of peptides predicted to bind to previously untested HLA-I molecules, cross-validation, and retrospective prediction of known HIV immune epitopes and endogenous presented peptides, all successfully validate this method. We further demonstrate that the method can be applied to perform a clustering analysis of MHC specificities and suggest using this clustering to select particularly informative novel MHC molecules for future biochemical and functional analysis. Encompassing all HLA molecules, this high-throughput computational method lends itself to epitope searches that are not only genome- and pathogen-wide, but also HLA-wide. Thus, it offers a truly global analysis of immune responses supporting rational development of vaccines and immunotherapy. It also promises to provide new basic insights into HLA structure-function relationships. The method is available at http://www.cbs.dtu.dk/services/NetMHCpan.
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DOI：
10.1073/pnas.89.22.10915
发表时间：
1992-11-15
影响因子：
11.1
作者：
HENIKOFF, S;HENIKOFF, JG
通讯作者：
HENIKOFF, JG
影响因子：
4.4
作者：
Doytchinova, IA;Guan, PP;Flower, DR
通讯作者：
Flower, DR
影响因子：
64.8
作者：
FALK, K;ROTZSCHKE, O;RAMMENSEE, HG
通讯作者：
RAMMENSEE, HG
影响因子：
2.9
作者：
Bordner, AJ;Abagyan, R
通讯作者：
Abagyan, R
影响因子：
5.6
作者：
Gulukota, K;Sidney, J;DeLisi, C
通讯作者：
DeLisi, C