T cell receptor reversed polarity recognition of a self-antigen major histocompatibility complex
T cell receptor reversed polarity recognition of a self-antigen major histocompatibility complex
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DOI：
10.1038/ni.3271
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发表时间：
2015-11-01
影响因子：
30.5
通讯作者：
Rossjohn, Jamie
中科院分区：
文献类型：
--
作者：
Beringer, Dennis X.;Kleijwegt, Fleur S.;Rossjohn, Jamie
适应性免疫的核心是α - β - T细胞受体（TCR）与主要组织相容性复合体（MHC）分子呈现的肽之间的相互作用。可能反映了TCR-MHC的偏见和T细胞信号传导的限制，TCR普遍采用MHC顶部的规范极性。我们报道了两种tcr的结构，它们来源于人诱导的T调节（iT(reg)）细胞，与MHC II类分子络合，呈现胰岛素原衍生肽。与所有其他tcr -肽- mhc复合物结构相比，三元配合物显示1800极性反转。即iT(reg) TCR α链和β链分别被MHC II类α链和β链覆盖。然而，这种TCR相互作用引发了肽反应，mhc限制性T细胞信号。因此，TCR并不是“天生的”与MHC分子以一种刻板的方式相互作用以引发T细胞信号，这一发现从根本上挑战了我们对TCR识别的理解。
Central to adaptive immunity is the interaction between the alpha beta T cell receptor (TCR) and peptide presented by the major histocompatibility complex (MHC) molecule. Presumably reflecting TCR-MHC bias and T cell signaling constraints, the TCR universally adopts a canonical polarity atop the MHC. We report the structures of two TCRs, derived from human induced T regulatory (iT(reg)) cells, complexed to an MHC class II molecule presenting a proinsulin-derived peptide. The ternary complexes revealed a 1800 polarity reversal compared to all other TCR-peptide-MHC complex structures. Namely, the iT(reg) TCR alpha-chain and beta-chain are overlaid with the alpha-chain and beta-chain of MHC class II, respectively. Nevertheless, this TCR interaction elicited a peptide-reactive, MHC-restricted T cell signal. Thus TCRs are not 'hardwired' to interact with MHC molecules in a stereotypic manner to elicit a T cell signal, a finding that fundamentally challenges our understanding of TCR recognition.