Searching immunodominant epitopes prior to epidemic: HLA class II-restricted SARS-CoV spike protein epitopes in unexposed individuals.
Searching immunodominant epitopes prior to epidemic: HLA class II-restricted SARS-CoV spike protein epitopes in unexposed individuals.
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DOI：
10.1093/intimm/dxn124
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发表时间：
2009-01
影响因子：
4.4
通讯作者：
Kwok WW
中科院分区：
文献类型：
--
作者：
Yang J;James E;Roti M;Huston L;Gebe JA;Kwok WW
识别新出现和再次出现的感染性生物中的优势T细胞表位对于理解病原性免疫反应和潜在的疫苗设计是有价值的。然而，从患者或恢复期受试者身上获取样本的困难阻碍了这一方向的研究。我们展示了一种策略，四聚体引导的表位映射，可以通过使用来自没有接触过受感染生物的受试者的PBMC来识别特定的CD4+T细胞表位。在严重急性呼吸综合征冠状病毒(SARS-CoV)刺突蛋白中鉴定了16个人类白细胞抗原DR0401和14个人类白细胞抗原DR0701限制性表位。其中159-171、166-178、449-461和1083-1097是基于PBMC对完整的Spike蛋白刺激产生的强大的体外T细胞反应而确定的含有自然加工的免疫优势表位。这些免疫优势表位在用Spike蛋白免疫的转基因小鼠体内得到证实。此外，来自幼稚捐献者的表位特异性T细胞在相应的四聚体的再次刺激下分泌干扰素-γ和IL-13。我们的研究证明了一种策略，以确定潜在的免疫优势表位的新出现的传染病病原体之前，他们流行。
Identification of dominant T cell epitopes within newly emerging and re-emerging infectious organisms is valuable in understanding pathogenic immune responses and potential vaccine designs. However, difficulties in obtaining samples from patients or convalescent subjects have hampered research in this direction. We demonstrated a strategy, tetramer-guided epitope mapping, that specific CD4+ T cell epitopes can be identified by using PBMC from subjects that have not been exposed to the infectious organism. Sixteen HLA-DR0401- and 14 HLA-DR0701-restricted epitopes within spike protein of severe acute respiratory syndrome-coronavirus (SARS-CoV) were identified. Among these, spike protein residues 159–171, 166–178, 449–461 and 1083–1097 were identified to contain naturally processed immunodominant epitopes based on strong in vitro T cell responses of PBMC (as assayed by tetramer staining) to intact spike protein stimulation. These immunodominant epitopes were confirmed in vivo in HLA-DR0401 transgenic mice by immunizing with spike protein. Furthermore, the epitope-specific T cells from naive donors secreted IFN-γ and IL-13 upon re-stimulation with corresponding tetramers. Our study demonstrates a strategy to determine potential immunodominant epitopes for emerging infectious pathogens prior to their epidemic circulation.
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影响因子：
64.8
作者：
Li W;Moore MJ;Vasilieva N;Sui J;Wong SK;Berne MA;Somasundaran M;Sullivan JL;Luzuriaga K;Greenough TC;Choe H;Farzan M
通讯作者：
Farzan M
DOI：
10.1016/s0140-6736(03)13077-2
发表时间：
2003-04-19
期刊：
Lancet (London, England)
影响因子：
--
作者：
Peiris JS;Lai ST;Poon LL;Guan Y;Yam LY;Lim W;Nicholls J;Yee WK;Yan WW;Cheung MT;Cheng VC;Chan KH;Tsang DN;Yung RW;Ng TK;Yuen KY;SARS study group
通讯作者：
SARS study group
DOI：
10.1016/s0140-6736(03)13967-0
发表时间：
2003-07-26
期刊：
Lancet (London, England)
影响因子：
--
作者：
Kuiken T;Fouchier RA;Schutten M;Rimmelzwaan GF;van Amerongen G;van Riel D;Laman JD;de Jong T;van Doornum G;Lim W;Ling AE;Chan PK;Tam JS;Zambon MC;Gopal R;Drosten C;van der Werf S;Escriou N;Manuguerra JC;Stöhr K;Peiris JS;Osterhaus AD
通讯作者：
Osterhaus AD
影响因子：
15.9
作者：
Novak, EJ;Liu, AW;Kwok, WW
通讯作者：
Kwok, WW
影响因子：
5.4
作者：
Broer, R;Boson, B;Corver, J
通讯作者：
Corver, J