Epitope-specific TCRβ repertoire diversity imparts no functional advantage on the CD8+ T cell response to cognate viral peptides
Epitope-specific TCRβ repertoire diversity imparts no functional advantage on the CD8+ T cell response to cognate viral peptides
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DOI：
10.1073/pnas.0711682102
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发表时间：
2008-02-12
影响因子：
11.1
通讯作者：
Turner, Stephen J.
中科院分区：
文献类型：
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作者：
La Gruta, Nicole L.;Thomas, Paul G.;Turner, Stephen J.
TCR库多样性已令人信服地显示出促进CD 8（+）T细胞群体对突变病毒肽的响应性，从而防止病毒逃逸。然而，库多样性对CD 8（+）T细胞应答同源肽-MHC I类复合物（pMHC）识别的功能性的影响仍不清楚。在此，我们比较了C57 BL/6（B6）小鼠中三种甲型流感病毒表位特异性CD 8 + T细胞应答的TCR β链库：（DNP 366 -374）-N-B、D（B）PA（224-233）和最近描述的来源于流感病毒聚合酶B亚基+1阅读框的表位（残基62-70）（D（B）PB 1-F2（62））。与相应pMHC的相对抗原性相对应，并且与突出残基的位置无关，D（B）PA（224-）和D（B）PB 1-F2（62）特异性库具有相似的多样性，而（DNP 366）-N-B群体显著更窄。重要的是，对三种表位特异性应答的应答幅度、细胞毒性、TCR亲合力和细胞因子产生的平行分析显示，增加的T细胞库多样性没有赋予明显的功能优势。因此，尽管多样的库对于识别表位变体可能是重要的，但其对同源pMHC识别的应答的影响似乎很小。
TCR repertoire diversity has been convincingly shown to facilitate responsiveness of CD8(+) T cell populations to mutant virus peptides, thereby safeguarding against viral escape. However, the impact of repertoire diversity on the functionality of the CD8(+) T cell response to cognate peptide-MHC class I complex (pMHC) recognition remains unclear. Here, we have compared TCR beta chain repertoires of three influenza A epitope-specific CD8+ T cell responses in C57BL/6 (B6) mice: (DNP366-374)-N-b, D(b)PA(224-233), and a recently described epitope derived from the +1 reading frame of the influenza viral polymerase B subunit (residues 62-70) (D(b)PB1-F2(62)). Corresponding to the relative antigenicity of the respective pMHCs, and irrespective of the location of prominent residues, the D(b)PA(224-) and D(b)PB1-F2(62)-specific repertoires were similarly diverse, whereas the (DNP366)-N-b population was substantially narrower. importantly, parallel analysis of response magnitude, cytotoxicity, TCR avidity, and cytokine production for the three epitope-specific responses revealed no obvious functional advantage conferred by increased T cell repertoire diversity. Thus, whereas a diverse repertoire may be important for recognition of epitope variants, its effect on the response to cognate pMHC recognition appears minimal.