The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom;
The Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Midlothian, United Kingdom.
J Immunol. 2021 Oct 15;207(8):1965-1977. doi: 10.4049/jimmunol.2100331. Epub 2021 Sep 10.
Parasite-specific CD8 T cell responses play a key role in mediating immunity against in cattle (), 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 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 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 and identify Ags suitable for use in vaccine development.
寄生虫特异性 CD8 T 细胞反应在介导牛（）的免疫中起关键作用，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。本研究使用一种基于 CD4 T 细胞的高通量抗原鉴定系统，从免疫动物中筛选了一个包含约 40,000 个代表 499 个基因产物的合成肽文库。使用来自 12 头免疫牛的 CD4 T 细胞（代表 12 种 MHC Ⅱ类型）鉴定了 26 种抗原。与 CD8 T 细胞反应不同，后者集中于少数优势抗原，个体动物的 CD4 T 细胞反应可识别多种抗原。这些抗原具有不同的特性，但包括由两个多成员基因家族编码的蛋白：五种卤酸脱卤酶和五种端粒下编码的可变分泌蛋白。大多数抗原具有预测的信号肽和/或由大量转录基因编码，但这两个参数本身都不能可靠地预测抗原性。表位作图证实了 DR 或 DQ Ⅱ类等位基因的呈递，并且对可用的 基因组序列的比较表明，它们包括保守和多态性表位。用表达两种抗原的疫苗载体免疫动物，可诱导能够识别寄生细胞的 CD4 T 细胞反应。这项研究的结果为 诱导的 CD4 T 细胞反应提供了详细的见解，并确定了适合用于疫苗开发的抗原。
