Early establishment of diverse T cell receptor profiles for influenza-specific CD8+CD62Lhi memory T cells
Early establishment of diverse T cell receptor profiles for influenza-specific CD8+CD62Lhi memory T cells
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DOI：
10.1073/pnas.0603289103
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发表时间：
2006-06-13
影响因子：
11.1
通讯作者：
Doherty, Peter C.
中科院分区：
文献类型：
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作者：
Kedzierska, Katherine;Venturi, Vanessa;Doherty, Peter C.
对流感病毒(DNP366)-N-b和D(b)PA（224）表位的内源性原代CD8(+) T细胞应答的单细胞分析表明，携带“公共”或“共享”T细胞受体（TCRs）亚群的突出克隆型早期进入CD62L（hi）和CD62L（lo）群体。CD62L（lo）效应子分裂更多，并在收缩阶段迅速消除，而稳定的CD62Lhi记忆群体长期存在。反映了表达“私有”TCR的CD62Lhi小克隆的高频率，在CD62L(hi)CD8(+)D(b)NP(366)（+）集合中，每只小鼠的TCR多样性范围通常高出2倍(CD62L(hi)CD8(+)DbPA(224)(+))，从抗原激发后8到180天。因此，记忆CD8(+)CD62L(hi) T细胞前体从一开始就分离成表达“最适合”和“次优”TCR特征的群体，此后这种模式一直保持稳定。因此，我们的分析表明，在CD8(+)CD62L（hi）亚群中早期建立流感特异性记忆可以保持克隆多样性，并防止少数公共或共享克隆的“优势”。
Single-cell analysis of endogenous, primary CD8(+) T cell responses to the influenza (DNP366)-N-b and D(b)PA(224) epitopes indicates that prominent clonotypes bearing "public" or "shared" T cell receptors (TCRs) subset early into CD62L(hi) and CD62L(lo) populations. The CD62L(lo) effectors divide more and are rapidly eliminated during the contraction phase, whereas stable CD62Lhi memory populations persist in the long-term. Reflecting the high frequency of small CD62Lhi clones expressing "private" TCRs, the TCR diversity range per mouse is generally two times higher within the CD62L(hi)CD8(+)D(b)NP(366)(+) set (1.6 times higher for CD62L(hi)CD8(+)DbPA(224)(+)) from 8 to > 180 days after antigen challenge. Memory CD8(+)CD62L(hi) T cell precursors thus segregate from the outset into populations expressing "best-fit" and "suboptimal" TCR characteristics, with this pattern being maintained stably thereafter. Hence, our analysis suggests that early establishment of influenza-specific memory within the CD8(+)CD62L(hi) subset preserves clonal diversity and prevents "overdominance" by a few public, or shared, clones.