Suppr超能文献

修复不相关的 TCRα 链揭示了 TCRβ 多样性对于病毒特异性 CD8+ T 细胞的最佳 TCRαβ 配对和功能的重要性。

Fixing an irrelevant TCR alpha chain reveals the importance of TCR beta diversity for optimal TCR alpha beta pairing and function of virus-specific CD8+ T cells.

机构信息

Department of Microbiology and Immunology, University of Melbourne, Vic 3010, Australia.

出版信息

Eur J Immunol. 2010 Sep;40(9):2470-81. doi: 10.1002/eji.201040473.

Abstract

TCR repertoire diversity can influence the efficacy of CD8(+) T-cell populations, with greater breadth eliciting better protection. We analyzed TCR beta diversity and functional capacity for influenza-specific CD8(+) T cells expressing a single TCR alpha chain. Mice (A7) transgenic for the H2K(b)OVA(257-264)-specific V alpha 2.7 TCR were challenged with influenza to determine how fixing this "irrelevant" TCR alpha affects the "public" and restricted D(b)NP(366) (+)CD8(+) versus the "private" and diverse D(b)PA(224) (+)CD8(+) responses. Though both D(b)NP(366) (+)CD8(+) and D(b)PA(224) (+)CD8(+) sets are generated in virus-primed A7 mice, the constrained D(b)NP(366) (+)CD8(+) population lacked the characteristic, public TCRV beta 8.3, and consequently was reduced in magnitude and pMHC-I avidity. For the more diverse D(b)PA(224) (+)CD8(+) T cells, this particular forcing led to a narrowing and higher TCR beta conservation of the dominant V beta 7, though the responses were of comparable magnitude to C57BL/6J controls. Interestingly, although both the TCR beta diversity and the cytokine profiles were reduced for the D(b)NP(366) (+)CD8(+) and D(b)PA(224) (+)CD8(+) sets in spleen, the latter measure of polyfunctionality was comparable for T cells recovered from the infected lungs of A7 and control mice. Even "sub-optimal" TCR alpha beta pairs can operate effectively when exposed in a milieu of high virus load. Thus, TCR beta diversity is important for optimal TCR alpha beta pairing and function when TCR alpha is limiting.

摘要

T 细胞受体(TCR)多样性可影响 CD8(+)T 细胞群体的疗效,更广泛的多样性可产生更好的保护作用。我们分析了表达单一 TCRα链的流感特异性 CD8(+)T 细胞的 TCRβ多样性和功能能力。用流感病毒对 H2K(b)OVA(257-264)-特异性 Vα2.7 TCR 的 A7 转基因小鼠进行了挑战,以确定固定这种“无关”TCRα如何影响“公共”和受限的 D(b)NP(366) (+)CD8(+)与“私有”和多样化的 D(b)PA(224) (+)CD8(+)反应。尽管在病毒引发的 A7 小鼠中都产生了 D(b)NP(366) (+)CD8(+)和 D(b)PA(224) (+)CD8(+)细胞群,但受限的 D(b)NP(366) (+)CD8(+)群体缺乏特征性的公共 TCRVβ8.3,因此其数量和 pMHC-I 亲和力均降低。对于更为多样化的 D(b)PA(224) (+)CD8(+)T 细胞,这种特殊的限制导致主导的 Vβ7 的 TCRβ趋同和更高的保守性,尽管其反应的幅度与 C57BL/6J 对照相当。有趣的是,尽管 D(b)NP(366) (+)CD8(+)和 D(b)PA(224) (+)CD8(+)细胞群的 TCRβ多样性和细胞因子谱在脾脏中均降低,但从 A7 和对照小鼠感染肺中回收的 T 细胞的后一多功能性指标相当。即使是“次优”的 TCRαβ 对也可以在高病毒载量的环境中有效运作。因此,当 TCRα受到限制时,TCRβ多样性对于最佳 TCRαβ配对和功能很重要。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验