T cell receptor cross-reactivity directed by antigen-dependent tuning of peptide-MHC molecular flexibility.
T cell receptor cross-reactivity directed by antigen-dependent tuning of peptide-MHC molecular flexibility.
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DOI：
10.1016/j.immuni.2009.11.003
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发表时间：
2009-12-18
期刊：
影响因子：
32.4
通讯作者：
Baker BM
中科院分区：
文献类型：
--
作者：
Borbulevych OY;Piepenbrink KH;Gloor BE;Scott DR;Sommese RF;Cole DK;Sewell AK;Baker BM
Tell介导的免疫需要T细胞受体（TCR）交叉反应性，其背后的机制仍未完全阐明。αβ TCR A6识别由人I类MHC分子HLA-A2呈递的Tax（LLFGYPVYV）和Tel 1 p（MLWGYLQYV）肽。在这里，我们发现，虽然这两种配体是理想的结构模拟物，但它们与A6形成了实质上不同的界面，在肽、TCR和出乎意料的MHC分子中具有构象差异。Tax和Tel 1 p三元复合物之间的差异不能从游离肽-MHC结构预测，并且与传统的诱导配合机制不一致。相反，这些差异归因于Tel 1 p-HLA-A2中存在的肽和MHC分子运动，而Tax-HLA-A2中不存在。因此，Tax和Tel 1 p肽对HLA-A2动态特性的差异“调节”促进了交叉识别，并影响了免疫系统受体如何呈现和容纳结构多样性。
Tell mediated immunity requires T cell receptor (TCR) cross-reactivity, the mechanisms behind which remain incompletely elucidated. The αβ TCR A6 recognizes both the Tax (LLFGYPVYV) and Tel1p (MLWGYLQYV) peptides presented by the human class I MHC molecule HLA-A2. Here we found that although the two ligands are ideal structural mimics, they form substantially different interfaces with A6, with conformational differences in the peptide, the TCR, and unexpectedly, the MHC molecule. The differences between the Tax and Tel1p ternary complexes could not be predicted from the free peptide-MHC structures and are inconsistent with a traditional induced-fit mechanism. Instead, the differences were attributable to peptide and MHC molecular motion present in Tel1p-HLA-A2 but absent in Tax-HLA-A2. Differential “tuning” of the dynamic properties of HLA-A2 by the Tax and Tel1p peptides thus facilitates cross-recognition and impacts how structural diversity can be presented to and accommodated by receptors of the immune system.
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DOI：
10.1002/prot.340110305
发表时间：
1991-01-01
期刊：
PROTEINS-STRUCTURE FUNCTION AND GENETICS
影响因子：
--
作者：
ICHIYE, T;KARPLUS, M
通讯作者：
KARPLUS, M
影响因子：
64.5
作者：
Colf, Leremy A.;Bankovich, Alexander J.;Garcia, K. Christopher
通讯作者：
Garcia, K. Christopher
影响因子：
8
作者：
Kim, MK;Kang, YK
通讯作者：
Kang, YK
DOI：
10.1093/protein/gzg087
发表时间：
2003-09-01
期刊：
PROTEIN ENGINEERING
影响因子：
--
作者：
Boulter, JM;Glick, M;Jakobsen, BK
通讯作者：
Jakobsen, BK
影响因子：
5.6
作者：
Febian, Heinz;Huser, Hans;Naumann, Dieter
通讯作者：
Naumann, Dieter