The serodominant secreted effector protein of Salmonella, SseB, is a strong CD4 antigen containing an immunodominant epitope presented by diverse HLA class II alleles.
The serodominant secreted effector protein of Salmonella, SseB, is a strong CD4 antigen containing an immunodominant epitope presented by diverse HLA class II alleles.
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DOI：
10.1111/imm.12327
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发表时间：
2014-11
期刊：
影响因子：
6.4
通讯作者：
Boyton RJ
中科院分区：
文献类型：
--
作者：
Reynolds CJ;Jones C;Blohmke CJ;Darton TC;Goudet A;Sergeant R;Maillere B;Pollard AJ;Altmann DM;Boyton RJ
考虑到人类沙门氏菌感染的全球负担以及CD4T细胞对这种细胞内感染的免疫可能做出的贡献，对沙门氏菌病保护性T细胞反应的详细表征是一个迫切而未得到满足的需求。在先前针对抗原阵列筛选患者血清的研究中，SSEB是值得注意的适应性免疫的血清显性靶点，与血清阳性患者相比，SSEB在HIV血清阴性患者中诱导显著提高的抗体反应。SSEB是一种分泌性蛋白，是EspA超家族的一部分，定位于细菌表面，是沙门氏菌致病岛2编码的III型分泌系统(T3SS)易位的一部分。我们在这里证明了SSEB也是CD4T细胞免疫的靶标，在人类志愿者实验感染后产生了实质性的应答，大约有0.1%的外周血细胞对SSEB有应答。人类白细胞抗原-DR/多肽结合研究表明，该蛋白含有多种多肽，能够与多种不同的人类白细胞抗原-DR等位基因结合。其中，11肽(P11)在人类白细胞抗原DR1和人类白细胞抗原DR4转基因小鼠的免疫反应中均显示含有免疫优势的CD4表位。对人类供体的反应分析表明，免疫集中在p11和多肽2的另一个表位上。SSEB反应性CD4T细胞的高频率和对不同HLA型的广泛适用性，加上先前在小鼠攻击实验中观察到的血清优势和保护性疫苗接种，使SSEB成为下一代沙门氏菌疫苗的可能候选者。
Detailed characterization of the protective T-cell response in salmonellosis is a pressing unmet need in light of the global burden of human Salmonella infections and the likely contribution of CD4 T cells to immunity against this intracellular infection. In previous studies screening patient sera against antigen arrays, SseB was noteworthy as a serodominant target of adaptive immunity, inducing significantly raised antibody responses in HIV-seronegative compared with seropositive patients. SseB is a secreted protein, part of the Espa superfamily, localized to the bacterial surface and forming part of the translocon of the type III secretion system (T3SS) encoded by Salmonella pathogenicity island 2. We demonstrate here that SseB is also a target of CD4 T-cell immunity, generating a substantial response after experimental infection in human volunteers, with around 0·1% of the peripheral repertoire responding to it. HLA-DR/peptide binding studies indicate that this protein encompasses a number of peptides with ability to bind to several different HLA-DR alleles. Of these, peptide 11 (p11) was shown in priming of both HLA-DR1 and HLA-DR4 transgenic mice to contain an immunodominant CD4 epitope. Analysis of responses in human donors showed immunity focused on p11 and another epitope in peptide 2. The high frequency of SseB-reactive CD4 T cells and the broad applicability to diverse HLA genotypes coupled with previous observations of serodominance and protective vaccination in mouse challenge experiments, make SseB a plausible candidate for next-generation Salmonella vaccines.
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影响因子：
168.9
作者：
Feasey, Nicholas A.;Dougan, Gordon;Kingsley, Robert A.;Heyderman, Robert S.;Gordon, Melita A.
通讯作者：
Gordon, Melita A.
DOI：
10.1084/jem.181.3.867
发表时间：
1995-03-01
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Altmann DM;Douek DC;Frater AJ;Hetherington CM;Inoko H;Elliott JI
通讯作者：
Elliott JI
影响因子：
32.4
作者：
Moon, James J.;Chu, H. Hamlet;Jenkins, Marc K.
通讯作者：
Jenkins, Marc K.
影响因子：
1.6
作者：
Prando, Carolina;Samarina, Arina;Casanova, Jean-Laurent
通讯作者：
Casanova, Jean-Laurent
影响因子：
1.9
作者：
Ahmad, Kaashif Aqeeb;Khan, Liaqat Hayat;Bhutta, Zulfiqar A.
通讯作者：
Bhutta, Zulfiqar A.