T Cell Immunity to the Alkyl Hydroperoxide Reductase of Burkholderia pseudomallei: A Correlate of Disease Outcome in Acute Melioidosis.
T Cell Immunity to the Alkyl Hydroperoxide Reductase of Burkholderia pseudomallei: A Correlate of Disease Outcome in Acute Melioidosis.
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DOI：
10.4049/jimmunol.1402862
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发表时间：
2015-05-15
期刊：
影响因子：
--
通讯作者：
Boyton R
中科院分区：
文献类型：
--
作者：
Reynolds C;Goudet A;Jenjaroen K;Sumonwiriya M;Rinchai D;Musson J;Overbeek S;Makinde J;Quigley K;Manji J;Spink N;Yos P;Wuthiekanun V;Bancroft G;Robinson J;Lertmemongkolchai G;Dunachie S;Maillere B;Holden M;Altmann D;Boyton R
目前迫切需要更好地了解假性伯克霍尔德菌的适应性免疫，伯克霍尔德菌是类鼻疽病的病原体，在东南亚和北澳大利亚患者中经常与败血症或死亡有关。这些地区的公共卫生议程和对生物威胁的关切推动了确定疫苗目标的必要性。在一些细胞内细菌病原体中，烷基氢过氧化物酶还原酶作为宿主氧化应激反应的一部分被上调，它们可以刺激强适应性免疫。我们发现假假芽孢杆菌的烷基氢过氧化物酶还原酶（AhpC）对人源化的HLA转基因小鼠和血清阳性的人类供体的T细胞具有很强的免疫原性。一些T细胞表位，如p6，能够结合多种HLA II类异源二聚体，并在小鼠和人类中刺激强大的T细胞免疫。重要的是，感染后存活的急性类鼻疽患者对AhpC表现出更强的T细胞反应。虽然AhpC序列在全球假假芽孢杆菌临床分离株中几乎是不变的，但柬埔寨分离株仅在p6 T细胞表位的c端截断上有所不同，这提高了宿主免疫选择的可能性。这种变异肽实际上不能刺激T细胞免疫。对于一种感染，关于T细胞免疫在防御中的中心地位一直存在争议，这些观察结果支持T细胞免疫对AhpC在疾病保护中的作用。
There is an urgent need for a better understanding of adaptive immunity to Burkholderia pseudomallei, the causative agent of melioidosis that is frequently associated with sepsis or death in patients in Southeast Asia and Northern Australia. The imperative to identify vaccine targets is driven both by the public health agenda in these regions and biological threat concerns. In several intracellular bacterial pathogens, alkyl hydroperoxidase reductases are upregulated as part of the response to host oxidative stress, and they can stimulate strong adaptive immunity. We show that alkyl hydroperoxidase reductase (AhpC) of B. pseudomallei is strongly immunogenic for T cells of ‘humanized’ HLA transgenic mice and seropositive human donors. Some T cell epitopes, such as p6, are able to bind diverse HLA class II heterodimers and stimulate strong T cell immunity in mice and humans. Importantly, patients with acute melioidosis who survive infection show stronger T cell responses to AhpC relative to those who do not. Although the sequence of AhpC is virtually invariant among global B. pseudomallei clinical isolates, a Cambodian isolate varies only in C-terminal truncation of the p6 T cell epitope, raising the possibility of selection by host immunity. This variant peptide is virtually unable to stimulate T cell immunity. For an infection in which there has been debate about centrality of T cell immunity in defense, these observations support a role for T cell immunity to AhpC in disease protection.
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DOI：
10.4269/ajtmh.2005.73.1165
发表时间：
2005-12-01
影响因子：
3.3
作者：
Chierakul, W;Wuthiekanun, V;Peacock, SJ
通讯作者：
Peacock, SJ
DOI：
10.1073/pnas.91.15.7017
发表时间：
1994-07-19
影响因子：
11.1
作者：
CHAE, HZ;ROBISON, K;RHEE, SG
通讯作者：
RHEE, SG
影响因子：
6.4
作者：
Reynolds CJ;Jones C;Blohmke CJ;Darton TC;Goudet A;Sergeant R;Maillere B;Pollard AJ;Altmann DM;Boyton RJ
通讯作者：
Boyton RJ
影响因子：
6.4
作者：
Price EP;Sarovich DS;Mayo M;Tuanyok A;Drees KP;Kaestli M;Beckstrom-Sternberg SM;Babic-Sternberg JS;Kidd TJ;Bell SC;Keim P;Pearson T;Currie BJ
通讯作者：
Currie BJ
影响因子：
6.7
作者：
Ascough, Stephanie;Ingram, Rebecca J.;Altmann, Daniel M.
通讯作者：
Altmann, Daniel M.