T Cell Receptor Clonotype Influences Epitope Hierarchy in the CD8+T Cell Response to Respiratory Syncytial Virus Infection
T Cell Receptor Clonotype Influences Epitope Hierarchy in the CD8+T Cell Response to Respiratory Syncytial Virus Infection
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DOI：
10.1074/jbc.m110.191437
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发表时间：
2011-02-01
影响因子：
4.8
通讯作者：
Graham, Barney S.
中科院分区：
文献类型：
--
作者：
Billam, Padma;Bonaparte, Kathryn L.;Graham, Barney S.
CD 8 + T细胞应答对于识别和解决病毒感染很重要。为了更好地了解病毒特异性T细胞反应的选择和层次，我们比较了呼吸道合胞病毒感染小鼠的亲本和杂交株的T细胞受体（TCR）克隆型。BALB/c中的K（d）M2（82-90）（SYIGSINNI）和C57 B1/6中的（DM 187 -195）-M-b（NAITNAKII）都是亲本菌株中的优势表位，但呈现不同的层次，在杂交CB 6 F1/J小鼠中，K（d）M2（82-90）对（DM 187 -195）-M-b是显性的。显性K（d）M2（82-90）反应相对公开，主要限于BALB/c和杂交小鼠中高度流行的V β 13.2，而C57 BL/6小鼠中的（DM 187 -195）-M-b反应相对私密，涉及多种V β亚型，其中一些在杂交小鼠中丢失。在（DM 187 -195）-M-b应答中TCR CDR 3序列的显著频率具有由有限数量的重组策略形成的独特的“（D/E）WG”基序。优势表位的建模表明其结构平坦、无特征，但（DM 187 -195）-M-b显示由Lys形成的独特结构（7）。这些数据表明，在流行的V β基因中常见的重组事件可能在T细胞应答中提供数量优势，并且不同的表位结构可能对成功的TCR选择施加更有限的选择。确定表位结构如何解释以告知T细胞功能将改善未来基于基因的疫苗的设计。
CD8+ T cell responses are important for recognizing and resolving viral infections. To better understand the selection and hierarchy of virus-specific T cell responses, we compared the T cell receptor (TCR) clonotype in parent and hybrid strains of respiratory syncytial virus-infected mice. K(d)M2(82-90) (SYIGSINNI) in BALB/c and (DM187-195)-M-b (NAITNAKII) in C57B1/6 are both dominant epitopes in parent strains but assume a distinct hierarchy, with K(d)M2(82-90) dominant to (DM187-195)-M-b in hybrid CB6F1/J mice. The dominant K(d)M2(82-90) response is relatively public and is restricted primarily to the highly prevalent V beta 13.2 in BALB/c and hybrid mice, whereas (DM187-195)-M-b responses in C57BL/6 mice are relatively private and involve multiple V beta subtypes, some of which are lost in hybrids. A significant frequency of TCR CDR3 sequences in the (DM187-195)-M-b response have a distinct "(D/E) WG" motif formed by a limited number of recombination strategies. Modeling of the dominant epitope suggested a flat, featureless structure, but (DM187-195)-M-b showed a distinctive structure formed by Lys(7). The data suggest that common recombination events in prevalent V beta genes may provide a numerical advantage in the T cell response and that distinct epitope structures may impose more limited options for successful TCR selection. Defining how epitope structure is interpreted to inform T cell function will improve the design of future gene-based vaccines.