Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02142, USA.
Proc Natl Acad Sci U S A. 2012 Mar 20;109(12):4580-5. doi: 10.1073/pnas.1201586109. Epub 2012 Mar 7.
Algorithms derived from measurements of short-peptide (8-10 mers) binding to class I MHC proteins suggest that the binding groove of a class I MHC protein, such as K(b), can bind well over 1 million different peptides with significant affinity (<500 nM), a level of ligand-binding promiscuity approaching the level of heat shock protein binding of unfolded proteins. MHC proteins can, nevertheless, discriminate between similar peptides and bind many of them with high (nanomolar) affinity. Some insights into this high-promiscuity/high-affinity behavior and its impact on immunodominant peptides in T-cell responses to some infections and vaccination are suggested by results obtained here from testing a model developed to predict the number of cell surface peptide-MHC complexes that form on cells exposed to extracellular (exogenous) peptides.
从对短肽（8-10 个氨基酸）与 I 类 MHC 蛋白结合的测量中推导出的算法表明，I 类 MHC 蛋白（如 K(b)）的结合槽可以很好地结合超过 100 万个具有显著亲和力（<500nM）的不同肽，这种配体结合的混杂性接近未折叠蛋白与热休克蛋白结合的水平。然而，MHC 蛋白可以区分相似的肽，并以高亲和力（纳摩尔）结合其中许多肽。通过测试一个用于预测暴露于细胞外（外源性）肽的细胞表面上形成的肽-MHC 复合物数量的模型，获得的结果表明，对这种高混杂性/高亲和力行为及其对某些感染和疫苗接种的 T 细胞反应中的免疫优势肽的影响有了一些了解。
