Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection.
Public clonotype usage identifies protective Gag-specific CD8+ T cell responses in SIV infection.
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DOI：
10.1084/jem.20081127
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发表时间：
2009-04-13
期刊：
影响因子：
--
通讯作者：
Douek DC
中科院分区：
文献类型：
--
作者：
Price DA;Asher TE;Wilson NA;Nason MC;Brenchley JM;Metzler IS;Venturi V;Gostick E;Chattopadhyay PK;Roederer M;Davenport MP;Watkins DI;Douek DC
尽管迫切需要艾滋病疫苗，但艾滋病毒保护性免疫的决定因素仍然隐藏在复杂的适应性免疫反应中。我们剖析了原发性 SIV 感染的 Mamu-A*01+ 恒河猴中免疫显性病毒特异性 CD8+ T 细胞群，以阐明个体成分克隆型水平上的有效免疫标志，这些克隆型是根据不同 T 细胞受体 (TCR) 的表达来识别的。公共克隆型的数量（定义为表达相同 TCR β 链氨基酸序列并在多个个体中重复出现的克隆型）数量，包含在特异于生物学限制的 Gag CM9（CTPYDINQM；残基 181-189）表位的急性期 CD8+ T 细胞群中，与病毒载量设定点呈负相关。这种独立的分子保护特征在一项前瞻性疫苗试验中得到了证实，其中克隆型参与由抗原的性质决定，而不是暴露的背景，并且公共克隆型的使用与表位变体的识别增强相关。因此，保护性 CD8+ T 细胞群内抗原特异性克隆型招募的模式是艾滋病病毒感染中疫苗功效和生物学结果的预后指标。
Despite the pressing need for an AIDS vaccine, the determinants of protective immunity to HIV remain concealed within the complexity of adaptive immune responses. We dissected immunodominant virus-specific CD8+ T cell populations in Mamu-A*01+ rhesus macaques with primary SIV infection to elucidate the hallmarks of effective immunity at the level of individual constituent clonotypes, which were identified according to the expression of distinct T cell receptors (TCRs). The number of public clonotypes, defined as those that expressed identical TCR β-chain amino acid sequences and recurred in multiple individuals, contained within the acute phase CD8+ T cell population specific for the biologically constrained Gag CM9 (CTPYDINQM; residues 181–189) epitope correlated negatively with the virus load set point. This independent molecular signature of protection was confirmed in a prospective vaccine trial, in which clonotype engagement was governed by the nature of the antigen rather than the context of exposure and public clonotype usage was associated with enhanced recognition of epitope variants. Thus, the pattern of antigen-specific clonotype recruitment within a protective CD8+ T cell population is a prognostic indicator of vaccine efficacy and biological outcome in an AIDS virus infection.
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DOI：
10.1084/jem.20070784
发表时间：
2007-10-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Almeida JR;Price DA;Papagno L;Arkoub ZA;Sauce D;Bornstein E;Asher TE;Samri A;Schnuriger A;Theodorou I;Costagliola D;Rouzioux C;Agut H;Marcelin AG;Douek D;Autran B;Appay V
通讯作者：
Appay V
影响因子：
4.4
作者：
Charini, WA;Kuroda, MJ;Letvin, NL
通讯作者：
Letvin, NL
DOI：
10.1073/pnas.0711682102
发表时间：
2008-02-12
影响因子：
11.1
作者：
La Gruta, Nicole L.;Thomas, Paul G.;Turner, Stephen J.
通讯作者：
Turner, Stephen J.
影响因子：
15.3
作者：
BURROWS, SR;SILINS, SL;ARGAET, VP
通讯作者：
ARGAET, VP
影响因子：
64.8
作者：
Champagne, P;Ogg, GS;Pantaleo, G
通讯作者：
Pantaleo, G