T-cell receptor (TCR) recognition of the myelin basic protein (MBP) peptide presented by major histocompatibility complex (MHC) protein HLA-DR2a, one of the MHC class II alleles associated with multiple sclerosis, is highly variable. Interactions in the trimolecular complex between the TCR of the MBP83-99-specific T cell clone 3A6 with the MBP-peptide/HLA-DR2a (abbreviated TCR/pMHC) lead to substantially different proliferative responses when comparing the wild-type decapeptide MBP90-99 and a superagonist peptide, which differs mainly in the residues that point toward the TCR. Here, we investigate the influence of the peptide sequence on the interface and intrinsic plasticity of the TCR/pMHC trimolecular and pMHC bimolecular complexes by molecular dynamics simulations. The intermolecular contacts at the TCR/pMHC interface are similar for the complexes with the superagonist and the MBP self-peptide. The orientation angle between TCR and pMHC fluctuates less in the complex with the superagonist peptide. Thus, the higher structural stability of the TCR/pMHC tripartite complex with the superagonist peptide, rather than a major difference in binding mode with respect to the self-peptide, seems to be responsible for the stronger proliferative response.

中文翻译：

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与具有自肽的复合物相比，3A6-TCR /超激动剂/ HLA-DR2a复合物显示出相似的界面，并降低了柔韧性。

主要组织相容性复合物（MHC）蛋白HLA-DR2a是与多发性硬化症相关的MHC II类等位基因之一，它对髓鞘碱性蛋白（MBP）肽的T细胞受体（TCR）识别高度可变。当比较野生型十肽MBP90-99时，MBP83-99特异性T细胞克隆3A6的TCR与MBP肽/ HLA-DR2a（缩写为TCR / pMHC）之间的三分子复合物中的相互作用导致实质上不同的增殖反应。和一种超激动剂肽，主要区别在于指向TCR的残基。在这里，我们通过分子动力学模拟研究了肽序列对TCR / pMHC三分子和pMHC双分子复合物的界面和固有可塑性的影响。对于具有超激动剂和MBP自肽的复合物，TCR / pMHC界面处的分子间接触是相似的。在与超激动剂肽形成的复合物中，TCR和pMHC之间的取向角波动较小。因此，TCR / pMHC三方复合物与超激动剂肽的较高结构稳定性，而不是与自身肽的结合方式的主要差异，似乎是造成较强增殖反应的原因。