T cell receptor reversed polarity recognition of a self-antigen major histocompatibility complex

Beringer Dennis X.; Kleijwegt Fleur S.; Wiede Florian; van der Slik Arno R.; Loh Khai Lee; Petersen Jan; Dudek Nadine L.; Duinkerken Gaby; Laban Sandra; Joosten Antoinette; Vivian Julian P.; Chen Zhenjun; Uldrich Adam P.; Godfrey Dale I.; McCluskey James; Price David A.; Radford Kristen J.; Purcell Anthony W.; Nikolic Tatjana; Reid Hugh H.; Tiganis Tony; Roep Bart O.; Rossjohn Jamie

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T cell receptor reversed polarity recognition of a self-antigen major histocompatibility complex

机译：自身抗原主要组织相容性复合体的T细胞受体反极性识别

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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.

机译：适应性免疫的中心是主要组织相容性复合物（MHC）分子在αβT细胞受体（TCR）和肽之间的相互作用。大概反映了TCR-MHC偏向和T细胞信号传导的约束，TCR普遍采用MHC顶部的规范极性。我们报告了两个TCRs的结构，它们源自人类诱导的T调节（iT（reg））细胞，与呈现胰岛素原衍生肽的MHC II类分子复合。与所有其他TCR-肽-MHC复合物结构相比，三元复合物显示出1800极性反转。即，iT（reg）TCRα链和β链分别与II类MHC的α链和β链重叠。然而，这种TCR相互作用引发了肽反应性，MHC限制的T细胞信号。因此，TCR并非以固定的方式“硬连线”与MHC分子相互作用以引发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。

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《Nature immunology》 |2015年第11期|共9页
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Beringer Dennis X.; Kleijwegt Fleur S.; Wiede Florian; van der Slik Arno R.; Loh Khai Lee; Petersen Jan; Dudek Nadine L.; Duinkerken Gaby; Laban Sandra; Joosten Antoinette; Vivian Julian P.; Chen Zhenjun; Uldrich Adam P.; Godfrey Dale I.; McCluskey James; Price David A.; Radford Kristen J.; Purcell Anthony W.; Nikolic Tatjana; Reid Hugh H.; Tiganis Tony; Roep Bart O.; Rossjohn Jamie;
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正文语种 eng
中图分类医学免疫学;
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1. T cell receptor reversed polarity recognition of a self-antigen major histocompatibility complex [J] . Beringer Dennis X., Kleijwegt Fleur S., Wiede Florian, Nature immunology . 2015,第11期

机译：自身抗原主要组织相容性复合体的T细胞受体反极性识别
2. Role of the major histocompatibility complex in T cell activation of B cell subpopulations. lyb-5(+) and lyb-5(-) B cell subpopulations differ in their requirement for major histocompatibility complex-restricted T cell recognition [J] . A Singer, PJ Morrissey, KS Hathcock, The Journal of Experomental Medicine . 1981,第2期

机译：主要组织相容性复合体在B细胞亚群的T细胞活化中的作用。 lyb-5（+）和lyb-5（-）B细胞亚群对主要组织相容性复合物限制T细胞识别的要求不同
3. Analysis of peptide binding patterns in different major histocompatibility complex/T cell receptor complexes using pigeon cytochrome c-specific T cell hybridomas. Evidence that a single peptide binds major histocompatibility complex in different conformations. [J] . H Bhayani, Y Paterson The Journal of Experomental Medicine . 1989,第5期

机译：使用鸽子细胞色素c特异性T细胞杂交瘤分析不同主要组织相容性复合物/ T细胞受体复合物中的肽结合模式。单个肽以不同构象结合主要组织相容性复合物的证据。
4. Invariant chain regulates the major histocompatibility complex class II peptide repertoire of cell-based cancer vaccines. [C] . Olesya Y. Chornoguz, Lydia Grmai, Alexei Gapeev, American Society for Mass Spectrometry Conference on Mass Spectrometry and Allied Topics . 2010

机译：不变链调节细胞基癌症疫苗的主要组织相容性复合体II类肽曲目。
5. Intercellular and intracellular events following the major histocompatibility complex-unrestricted T cell receptor recognition of a tumor-specific peptide epitope on the epithelial antigen MUC-1 [D] . Blander, Julie Margarian. 1997

机译：在上皮抗原Muc-1上的主要组织相容性复合物复合物的细胞间和细胞内事件识别肿瘤特异性肽表位
6. Major histocompatibility complex-restricted self recognition. A monoclonal anti-I-Ak reagent blocks helper T cell recognition of self major histocompatibility complex determinants [O] . 1980

机译：主要组织相容性复杂的自我识别。单克隆抗I-Ak试剂可阻断辅助T细胞对自身主要组织相容性复合物决定簇的识别
7. T cell receptor reversed polarity recognition of a self-antigen major histocompatibility complex [O] . Beringer Dennis X., Kleijwegt Fleur S., Wiede Florian, 2015

机译：自身抗原主要组织相容性复合体的T细胞受体反极性识别
8. Role of the Major Histocompatibility Complex in T Cell Activation of B Cell Subpopulations, Lyb-5(+) and Lyb-5(-) B Cell Subpopulations Differ in Their Requirement for Major Histocompatibility Complex-Restricted T Cell Recognition [R] . Singer, A., Morrissey, P. J., Hathcock, K. S., 1981

机译：主要组织相容性复合物在B细胞亚群，Lyb-5（+）和Lyb-5（ - ）B细胞亚群的T细胞活化中的作用不同于它们对主要组织相容性复杂限制性T细胞识别的要求

T cell receptor reversed polarity recognition of a self-antigen major histocompatibility complex

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