Dissecting mechanisms of immunodominance to the common tuberculosis antigens ESAT-6, CFP10, Rv2031c (hspX), Rv2654c (TB7.7), and Rv1038c (EsxJ).
Dissecting mechanisms of immunodominance to the common tuberculosis antigens ESAT-6, CFP10, Rv2031c (hspX), Rv2654c (TB7.7), and Rv1038c (EsxJ).
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DOI：
10.4049/jimmunol.1103556
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发表时间：
2012-05-15
期刊：
影响因子：
--
通讯作者：
Sette A
中科院分区：
文献类型：
--
作者：
Arlehamn CS;Sidney J;Henderson R;Greenbaum JA;James EA;Moutaftsi M;Coler R;McKinney DM;Park D;Taplitz R;Kwok WW;Grey H;Peters B;Sette A
结核病的诊断通常依赖于体外干扰素-γ释放分析Quantiferon-TB Gold-In-Tube和T-SPOT.TB。然而，对其诊断效用背后的免疫学机制的了解仍然不完整。因此，我们调查了这些检测中包括的结核抗原以及其他通常研究的抗原：ESAT-6、CFP10、Rv2031c、Rv2654c和Rv1038c的T细胞反应。来自潜伏感染个体的PBMC在体外ELISPOT试验中被用重叠的多肽跨越这些抗原的全部进行测试。我们发现，在体外反应性的患病率和大小方面存在显著差异，其中CFP10最占优势，其次是ESAT-6和Rv2654c几乎不活跃。Rv2031c和Rv1038c与中间反应模式相关。进一步的研究表明，低反应性并不是由于缺乏人类白细胞抗原结合肽，高反应性与识别少数离散的优势抗原区有关。不同的供体识别给定表位中的相同核心序列。在某些情况下，识别的表位受到单个特定的共同的HLA分子的限制(选择性限制)，而在另一些情况下，同一表位明显地受到多个HLA分子的混杂限制。对允许产生四聚体试剂的特定限制性人类白细胞抗原的定义表明，识别选择性或混杂限制性表位的表位特异性T细胞主要是T效应记忆(TMMMemory)。总之，这些结果强调了更明确定义的结核病诊断试剂的可行性。
Diagnosis of tuberculosis often relies on the ex vivo interferon gamma release assays QuantiFERON-TB Gold In-Tube and T-SPOT.TB. However, understanding of the immunological mechanisms underlying their diagnostic utility is still incomplete. Accordingly, we investigated T cell responses for the TB antigens included in the these assays and other commonly studied antigens; ESAT-6, CFP10, Rv2031c, Rv2654c, and Rv1038c. PBMC from latently infected individuals were tested in ex vivo ELISPOT assays with overlapping peptides spanning the entirety of these antigens. We found striking variations in prevalence and magnitude of ex vivo reactivity, with CFP10 being most dominant, followed by ESAT-6 and Rv2654c being virtually inactive. Rv2031c and Rv1038c were associated with intermediate patterns of reactivity. Further studies showed that low reactivity was not due to lack of HLA binding peptides, and high reactivity was associated with recognition of a few discrete dominant antigenic regions. Different donors recognized the same core sequence in a given epitope. In some cases the identified epitopes were restricted by a single specific common HLA molecule (selective restriction), while in other cases promiscuous restriction of the same epitope by multiple HLA molecules was apparent. Definition of the specific restricting HLA allowed to produce tetrameric reagents and show that epitope-specific T cells recognizing either selectively or promiscuously restricted epitopes were predominantly T effector memory (TEM). In conclusion, these results highlight the feasibility of more clearly defined TB diagnostic reagent.
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影响因子：
9.4
作者：
Brock, I;Weldingh, K;Andersen, P
通讯作者：
Andersen, P
影响因子：
3.1
作者：
Junqueira-Kipnis, AP;Turner, J;Orme, IM
通讯作者：
Orme, IM
DOI：
10.4049/jimmunol.1000801
发表时间：
2010-10-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Grotzke JE;Siler AC;Lewinsohn DA;Lewinsohn DM
通讯作者：
Lewinsohn DM
影响因子：
5.6
作者：
Gulukota, K;Sidney, J;DeLisi, C
通讯作者：
DeLisi, C
影响因子：
3.2
作者：
Kumar, Madhan;Meenakshi, N.;Raja, Alamelu
通讯作者：
Raja, Alamelu