Halling-Brown M, Quartey-Papafio R, Travers P J, Moss D S
Institute of Structural Molecular Biology, School of Crystallography, Birkbeck College, University of London, Malet Street, London, WC1E 7HX, UK.
Int J Immunogenet. 2006 Aug;33(4):289-95. doi: 10.1111/j.1744-313X.2006.00615.x.
Approximately 50 years ago it was found that inbred strains of mice were able to reject tumours and skin grafts from major histocompatibility complex (MHC) identical donors. They proposed that additional transplantation antigens must exist outside the MHC. These were described as minor histocompatibility antigens (mHAgs). Since then, related studies in humans have identified 16 human mHAgs. The aim of this work is to increase the number of known mHAgs by prediction of candidate minor histocompatibility loci by identifying coding single nucleotide polymorphisms (SNPs) where the amino acid variation lies within an MHC-binding peptide and alters the ability of that peptide to bind. We have developed an algorithm called SiPep which uses peptide sequences derived from the flanking regions of known non-synonymous SNPs, various MHC-binding and proteolytic cleavage evaluation methods and protein expression data to predict mHAgs. We have processed 45094 SNPs using the SiPep algorithm and have stored the results in a database called SNPBinder. The facilities to process submitted proteins through the SiPep algorithm as well as the SNPBinder database are available to the public. A set of peptides that are predicted as possible mHAgs by the SiPep algorithm have been tested using refolding assays and gel filtration and the results are presented in this paper. The SiPep tools and SNPBinder database are available free of charge via the internet. An HTML interface providing search facilities can be found at the following address: http://www.sipep.org/.
大约50年前，人们发现近交系小鼠能够排斥来自主要组织相容性复合体（MHC）相同供体的肿瘤和皮肤移植。他们提出，MHC之外必定存在其他移植抗原。这些被描述为次要组织相容性抗原（mHAgs）。从那时起，在人类中的相关研究已经鉴定出16种人类mHAgs。这项工作的目的是通过识别编码单核苷酸多态性（SNP）来预测候选次要组织相容性位点，从而增加已知mHAgs的数量，这些SNP的氨基酸变异位于MHC结合肽内并改变该肽的结合能力。我们开发了一种名为SiPep的算法，该算法使用从已知非同义SNP的侧翼区域衍生的肽序列、各种MHC结合和蛋白水解切割评估方法以及蛋白质表达数据来预测mHAgs。我们使用SiPep算法处理了45094个SNP，并将结果存储在一个名为SNPBinder的数据库中。通过SiPep算法处理提交的蛋白质以及SNPBinder数据库的功能可供公众使用。一组被SiPep算法预测为可能的mHAgs的肽已通过复性分析和凝胶过滤进行了测试，结果在本文中呈现。SiPep工具和SNPBinder数据库可通过互联网免费获取。提供搜索功能的HTML界面可在以下地址找到：http://www.sipep.org/
