A comparative approach linking molecular dynamics of altered peptide ligands and MHC with in vivo immune responses.
A comparative approach linking molecular dynamics of altered peptide ligands and MHC with in vivo immune responses.
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DOI：
10.1371/journal.pone.0011653
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发表时间：
2010-07-19
期刊：
影响因子：
3.7
通讯作者：
Epstein MM
中科院分区：
文献类型：
--
作者：
Knapp B;Omasits U;Schreiner W;Epstein MM
T淋巴细胞在MHC背景下识别肽是启动适应性免疫应答的关键步骤。然而，肽和MHC之间相互作用的分子本质以及它如何影响T细胞反应性尚未完全了解。我们分析了MHC II类（I-Au）限制的髓鞘碱性蛋白的11聚体肽与位置4处的氨基酸取代的相互作用的免疫学后果。这些突变肽在MHC结合亲和力、CD 4 + T细胞引发和改变肽诱导的实验性过敏性脑脊髓炎的严重程度方面不同。使用分子动力学，在高分辨率定量蛋白质的内在运动的计算方法，我们研究了肽结合后MHC的构象变化。我们发现，无论肽结合亲和力，MHC变形似乎影响共刺激，然后导致有效的T细胞引发和疾病诱导。虽然这项研究比较了在体内和分子动力学结果的三个改变肽配体，类似的复合物的进一步调查是必不可少的，以确定是否空间重排的肽-MHC和共刺激复合物是一个额外的水平的T细胞调节。
The recognition of peptide in the context of MHC by T lymphocytes is a critical step in the initiation of an adaptive immune response. However, the molecular nature of the interaction between peptide and MHC and how it influences T cell responsiveness is not fully understood. We analyzed the immunological consequences of the interaction of MHC class II (I-Au) restricted 11-mer peptides of myelin basic protein with amino acid substitutions at position 4. These mutant peptides differ in MHC binding affinity, CD4+ T cell priming, and alter the severity of peptide-induced experimental allergic encephalomyelitis. Using molecular dynamics, a computational method of quantifying intrinsic movements of proteins at high resolution, we investigated conformational changes in MHC upon peptide binding. We found that irrespective of peptide binding affinity, MHC deformation appears to influence costimulation, which then leads to effective T cell priming and disease induction. Although this study compares in vivo and molecular dynamics results for three altered peptide ligands, further investigation with similar complexes is essential to determine whether spatial rearrangement of peptide-MHC and costimulatory complexes is an additional level of T cell regulation.
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DOI：
10.1126/science.1169377
发表时间：
2009-04-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Smock RG;Gierasch LM
通讯作者：
Gierasch LM
影响因子：
2.1
作者：
Omasits, Ulrich;Knapp, Bernhard;Schreiner, Wolfgang
通讯作者：
Schreiner, Wolfgang
DOI：
10.1002/prot.340230412
发表时间：
1995-12-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
Frishman, D;Argos, P
通讯作者：
Argos, P
影响因子：
6.8
作者：
Hansson, T;Oostenbrink, C;van Gunsteren, WF
通讯作者：
van Gunsteren, WF
DOI：
10.1073/pnas.92.21.9510
发表时间：
1995-10-10
影响因子：
11.1
作者：
KUMAR, V;BHARDWAJ, V;SERCARZ, E
通讯作者：
SERCARZ, E