Peptide binding specificity of major histocompatibility complex class I resolved into an array of apparently independent subspecificities: Quantitation by peptide libraries and improved prediction of binding
Peptide binding specificity of major histocompatibility complex class I resolved into an array of apparently independent subspecificities: Quantitation by peptide libraries and improved prediction of binding
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DOI：
10.1002/eji.1830260836
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发表时间：
1996-08-01
影响因子：
5.4
通讯作者：
Buus, S
中科院分区：
文献类型：
--
作者：
Stryhn, A;Pedersen, LO;Buus, S
相当大的兴趣集中在了解主要组织相容性复合体（MHC）特异性是如何产生的，并表征MHC分子的特异性，最终目标是预测肽结合。我们已经使用了一种策略，其中将特定大小的所有可能的肽分布到位置扫描组合肽文库（PSCPL）中，以开发一种高效、通用和无偏倚的方法来解决MHC特异性。PSCPL的方法出现在定性和定量上级其他目前使用的战略。定量每个位置中任何氨基酸的平均效应，从而允许详细描述包括一级和二级锚残基的延伸肽结合基序。它还鉴定了不利的残基，发现这些残基在形成MHC I类特异性方面令人惊讶地重要。假设MHC I类特异性是很大程度上独立作用的亚位点的结果，未知肽的结合可以预测。相反，这表明MHC I类特异性由一系列以组合模式起作用的亚特异性组成。
Considerable interest has focused on understanding how major histocompatibility complex (MHC) specificity is generated and characterizing the specificity of MHC molecules with the ultimate goal being to predict peptide binding. We have used a strategy where all possible peptides of a particular size are distributed into positional scanning combinatorial peptide libraries (PSCPL) to develop a highly efficient, universal and unbiased approach to address MHC specificity. The PSCPL approach appeared qualitatively and quantitatively superior to other currently used strategies. The average effect of any amino acid in each position was quantitated, allowing a detailed description of extended peptide binding motifs including primary and secondary anchor residues. It also identified disfavored residues which were found to be surprisingly important in shaping MHC class I specificity. Assuming that MHC class I specificity is the result of largely independently acting subsites, the binding of unknown peptides could be predicted. Conversely, this argues that MHC class I specificities consist of an array of subspecificities acting in a combinatorial mode.