Naturally processed peptides longer than nine amino acid residues bind to the class I MHC molecule HLA-A2.1 with high affinity and in different conformations.
Naturally processed peptides longer than nine amino acid residues bind to the class I MHC molecule HLA-A2.1 with high affinity and in different conformations.
复制标题
DOI：
10.4049/jimmunol.152.6.2874
复制
发表时间：
1994-03
影响因子：
4.4
通讯作者：
Ye Chen;J. Sidney;S. Southwood;Andrea L. Cox;Kazuyasu Sakaguchi;Robert A. Henderson;Robert A. Henderson;Ettore Appella;D. F. Hunt;Alessandro Sette;V. Engelhard
中科院分区：
文献类型：
--
作者：
Ye Chen;J. Sidney;S. Southwood;Andrea L. Cox;Kazuyasu Sakaguchi;Robert A. Henderson;Robert A. Henderson;Ettore Appella;D. F. Hunt;Alessandro Sette;V. Engelhard
平衡结合实验用于直接测量自然加工的9-mer、10-mer和12-mer肽对人I类MHC分子HLA-A2.1的相对亲和力。这些肽的IC50值范围为11 ~ 214 nM。这些肽与HLA-A2.1之间的相互作用模式通过使用Asp取代可疑锚位点残基的肽来检测。无论长度如何，先前鉴定的相对于氨基末端位置2的Leu对肽结合至关重要。虽然羧基末端残基对9-聚肽的结合也很关键，但它对更长的肽的结合却不那么重要。靠近羧基端含有脂肪烃侧链的其他残基在肽结合中具有类似或更重要的作用。此外，3号位置的残基对于长肽的结合也很重要。数据表明，不同的自然产生的较长的肽可以以不同的构象与I类MHC分子结合。虽然其中一种构象类似于其他构象描述的扭结构象，但另一种构象将羧基端延伸到I类结合位点之外。MHC分子以不同构象容纳相同肽的能力似乎对免疫系统具有明显的优势。
An equilibrium binding assay was used to directly measure the relative affinities of naturally processed 9-mer, 10-mer, and 12-mer peptides for the human class I MHC molecule HLA-A2.1. The peptides exhibited a range of affinities with IC50 values of 11 to 214 nM. The mode of interaction between these peptides and HLA-A2.1 was examined using peptides in which Asp had been substituted for suspected anchor residues. Regardless of length, the previously identified Leu at position 2 relative to the amino terminus was critical for peptide binding. While the carboxyl terminal residue was also critical for the binding of a 9-mer peptide, it was much less important in the binding of longer peptides. Additional residues close to the carboxyl terminus that contained aliphatic hydrocarbon side chains were of similar or greater importance in peptide binding. In addition, residue at position 3 also appeared to be important for the binding of longer peptides. The data suggest that different naturally occurring longer peptides can bind in different conformations to class I MHC molecules. While one of these is similar to the kinked conformation described by others, another conformation would involve an extension of the carboxyl terminus out of the class I binding site. The ability of MHC molecules to accommodate the same peptide in different conformations would appear to have distinct advantages to the immune system.