Cross-clade detection of HIV-1-specific cytotoxic T lymphocytes does not reflect cross-clade antiviral activity
Cross-clade detection of HIV-1-specific cytotoxic T lymphocytes does not reflect cross-clade antiviral activity
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DOI：
10.1086/525281
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发表时间：
2008-02-01
影响因子：
6.4
通讯作者：
Yang, Otto O.
中科院分区：
文献类型：
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作者：
Bennett, Michael S.;Ng, Hwee L.;Yang, Otto O.
人类免疫缺陷病毒（HIV）-1对不同进化枝的遗传差异是基于细胞毒性T淋巴细胞（CTL）基于基于的疫苗发育的认真考虑。已经提出，CTL可以跨认识到来自不同进化枝的表位序列的证明是为单一疫苗提供希望。但是，通过评估识别外源肽的识别，可以产生跨片CTL数据。本研究比较了HIV-1特异性的CTL横层表位对外源载体肽的识别，并抑制了HIV-1感染的细胞。尽管CTL对前者的CTL显然具有广泛的交叉反应性，但CTL抑制具有相应表位序列的HIV-1菌株受到显着损害。 CTLs在非自学进化表位序列中的功能亲和力降低，表明CTL无法识别感染的内源性内源性细胞表面表位的水平，尽管识别出超义学外源性外源性添加的表位。这些数据强烈支持CTL的进化枝特异性抗病毒活性，并质疑标准方法评估跨层CTL活性或CTL抗病毒活性的有效性。
The genetic divergence of human immunodeficiency virus (HIV)-1 into distinct clades is a serious consideration for cytotoxic T lymphocyte (CTL)-based vaccine development. Demonstrations that CTLs can cross-recognize epitope sequences from different clades has been proposed as offering hope for a single vaccine. Cross-clade CTL data, however, have been generated by assessing recognition of exogenous peptides. The present study compares HIV-1-specific CTL cross-clade epitope recognition of exogenously loaded peptides with suppression of HIV-1 infected cells. Despite apparently broad cross-clade reactivity of CTLs against the former, CTL suppression of HIV-1 strains with corresponding epitope sequences is significantly impaired. The functional avidity of CTLs for nonautologous clade epitope sequences is diminished, suggesting that CTLs can fail to recognize levels of infected endogenously derived cell-surface epitopes despite recognizing supraphysiologic exogenously added epitopes. These data strongly support clade-specific antiviral activity of CTLs and call into question the validity of standard methods for assessing cross-clade CTL activity or CTL antiviral activity in general.