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CD4 T Cell Responses to Theileria parva in Immune Cattle Recognize a Diverse Set of Parasite Antigens Presented on the Surface of Infected Lymphoblasts
The Journal of Immunology ( IF 4.4 ) Pub Date : 2021-10-15 , DOI: 10.4049/jimmunol.2100331
W. Ivan Morrison , Adriana Aguado , Tara A. Sheldrake , Nicholas C. Palmateer , Olukemi O. Ifeonu , Kyle Tretina , Keith Parsons , Emilio Fenoy , Timothy Connelley , Morten Nielsen , Joana C. Silva

Parasite-specific CD8 T cell responses play a key role in mediating immunity against Theileria parva in cattle (Bos taurus), and there is evidence that efficient induction of these responses requires CD4 T cell responses. However, information on the antigenic specificity of the CD4 T cell response is lacking. The current study used a high-throughput system for Ag identification using CD4 T cells from immune animals to screen a library of ∼40,000 synthetic peptides representing 499 T. parva gene products. Use of CD4 T cells from 12 immune cattle, representing 12 MHC class II types, identified 26 Ags. Unlike CD8 T cell responses, which are focused on a few dominant Ags, multiple Ags were recognized by CD4 T cell responses of individual animals. The Ags had diverse properties, but included proteins encoded by two multimember gene families: five haloacid dehalogenases and five subtelomere-encoded variable secreted proteins. Most Ags had predicted signal peptides and/or were encoded by abundantly transcribed genes, but neither parameter on their own was reliable for predicting antigenicity. Mapping of the epitopes confirmed presentation by DR or DQ class II alleles and comparison of available T. parva genome sequences demonstrated that they included both conserved and polymorphic epitopes. Immunization of animals with vaccine vectors expressing two of the Ags demonstrated induction of CD4 T cell responses capable of recognizing parasitized cells. The results of this study provide detailed insight into the CD4 T cell responses induced by T. parva and identify Ags suitable for use in vaccine development.



中文翻译:

CD4 T 细胞对免疫牛中细小泰勒虫的反应识别出感染淋巴母细胞表面存在的多种寄生虫抗原

寄生虫特异性 CD8 T 细胞反应在介导对牛 ( Bos taurus ) 小泰勒虫的免疫中起关键作用,并且有证据表明这些反应的有效诱导需要 CD4 T 细胞反应。然而,缺乏关于 CD4 T 细胞反应的抗原特异性的信息。目前的研究使用高通量系统进行 Ag 鉴定,使用来自免疫动物的 CD4 T 细胞筛选代表 499 T. parva 的约 40,000 种合成肽库基因产品。使用来自 12 只免疫牛的 CD4 T 细胞,代表 12 种 MHC II 类,鉴定了 26 种抗原。与 CD8 T 细胞反应不同,CD8 T 细胞反应侧重于少数优势 Ag,多个 Ag 可被单个动物的 CD4 T 细胞反应识别。Ags 具有多种特性,但包括由两个多成员基因家族编码的蛋白质:五种卤酸脱卤酶和五种亚端粒编码的可变分泌蛋白。大多数 Ag 具有预测的信号肽和/或由大量转录的基因编码,但它们本身的两个参数都不能可靠地预测抗原性。通过 DR 或 DQ II 类等位基因确认表位的定位和可用T. parva 的比较基因组序列表明它们包括保守的和多态的表位。用表达两种 Ags 的疫苗载体对动物进行免疫接种证明诱导了能够识别寄生细胞的 CD4 T 细胞反应。这项研究的结果提供了对T. parva诱导的 CD4 T 细胞反应的详细了解,并确定了适用于疫苗开发的 Ags。

更新日期:2021-10-06
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