Characterization of the fine specificity of bovine CD8 T-Cell responses to defined antigens from the protozoan parasite Theileria parva
Characterization of the fine specificity of bovine CD8 T-Cell responses to defined antigens from the protozoan parasite Theileria parva
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DOI：
10.1128/iai.01244-07
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发表时间：
2008-02-01
影响因子：
3.1
通讯作者：
Taracha, Evans L. N.
中科院分区：
文献类型：
--
作者：
Graham, Simon P.;Pelle, Roger;Taracha, Evans L. N.
针对牛细胞内原生动物寄生虫微小泰勒虫的免疫已显示由CD 8 T细胞介导。来自T.已经鉴定了不同主要组织相容性复合体（MHC）基因型的细小免疫牛，提高了开发亚单位疫苗的前景。为了便于进一步剖析保护性CD 8 T细胞应答的特异性，并帮助评估对疫苗接种的应答，我们着手鉴定这些T细胞中识别的表位。parva抗原及其MHC限制性元件。6个T.成功鉴定了细小病毒抗原及其各自的MHC限制性元件。五个细胞毒性T淋巴细胞表位被发现限制由先前描述的等位基因的产品，和四个限制由四个新的限制性元件。分析的CD 8 T-细胞的抗原决定簇的牛携带的限制性元件和免疫活寄生虫组中的5个表位的反应表明，除了一个例外，表位一致地识别的动物的各自的基因型。将应答分析扩展到用在单独的疫苗构建体中递送的多种抗原免疫的动物。在24头免疫牛中的19头中检测到特异性CD 8 T细胞应答。所有应答牛均产生了对抗原特异性的应答，因为它们携带了已鉴定的限制性元件。相比之下，19头应答牛中只有8头显示出对抗原的应答，而这些应答牛不携带识别的限制性元件。这些数据表明，所鉴定的抗原在具有相应MHC基因型的动物中固有地占优势。
Immunity against the bovine intracellullar protozoan parasite Theileria parva has been shown to be mediated by CD8 T cells. Six antigens targeted by CD8 T cells from T. parva-immune cattle of different major histocompatibility complex (MHC) genotypes have been identified, raising the prospect of developing a subunit vaccine. To facilitate further dissection of the specificity of protective CD8 T-cell responses and to assist in the assessment of responses to vaccination, we set out to identify the epitopes recognized in these T. parva antigens and their MHC restriction elements. Nine epitopes in six T. parva antigens, together with their respective MHC restriction elements, were successfully identified. Five of the cytotoxic-T-lymphocyte epitopes were found to be restricted by products of previously described alleles, and four were restricted by four novel restriction elements. Analyses of CD8 T-cell responses to five of the epitopes in groups of cattle carrying the defined restriction elements and immunized with live parasites demonstrated that, with one exception, the epitopes were consistently recognized by animals of the respective genotypes. The analysis of responses was extended to animals immunized with multiple antigens delivered in separate vaccine constructs. Specific CD8 T-cell responses were detected in 19 of 24 immunized cattle. All responder cattle mounted responses specific for antigens for which they carried an identified restriction element. By contrast, only 8 of 19 responder cattle displayed a response to antigens for which they did not carry an identified restriction element. These data demonstrate that the identified antigens are inherently dominant in animals with the corresponding MHC genotypes.