The detection of long-lasting memory foot-and-mouth disease (FMD) virus serotype O-specific CD4+ T cells from FMD-vaccinated cattle by bovine major histocompatibility complex class II tetramer,Immunology

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The detection of long-lasting memory foot-and-mouth disease (FMD) virus serotype O-specific CD4+ T cells from FMD-vaccinated cattle by bovine major histocompatibility complex class II tetramer
Immunology ( IF 4.9 ) Pub Date : 2021-05-18 , DOI: 10.1111/imm.13367
Shuya Mitoma ₁ , Brigid Veronica Carr ₂ , Yongjie Harvey ₂ , Katy Moffat ₂ , Satoshi Sekiguchi ₁ , Bryan Charleston ₂ , Junzo Norimine ₁ , Julian Seago ₂

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Foot-and-mouth disease (FMD) is a highly contagious, economically devastating disease of cloven-hooved animals. The development of long-lasting effective FMD vaccines would greatly benefit the global FMD control programme. Deep analysis of adaptive immunity in cattle vaccinated against FMD is technically challenging due to the lack of species-specific tools. In this study, we aimed to identify CD4⁺ T-cell epitopes in the FMD virus (FMDV) capsid and to phenotype the CD4⁺ T cells that recognize them using bovine major histocompatibility complex (BoLA) class II tetramer. A BoLA class II tetramer based on the DRA/DRB3*020:02 allele and FMDV antigen-stimulated PBMCs from bovine vaccinates were used to successfully identify four epitopes in the FMDV capsid, three of which have not been previously reported; two epitopes were identified in the structural protein VP1, one in VP3 and one in VP4. Specificity of the three novel epitopes was confirmed by proliferation assay. All epitope-expanded T-cell populations produced IFN-γ in vitro, indicating a long-lasting Th1 cell phenotype after FMD vaccination. VP3-specific CD4⁺ T cells exhibited the highest frequency amongst the identified epitopes, comprising >0·004% of the CD4⁺ T-cell population. CD45RO⁺CCR7⁺ defined central memory CD4⁺ T-cell subpopulations were present in higher frequency in FMDV-specific CD4⁺ T-cell populations from FMD-vaccinated cattle ex vivo. This indicates an important role in maintaining cell adaptive immunity after FMD vaccination. Notably, FMDV epitope-loaded tetramers detected the presence of FMDV-specific CD4⁺ T cells in bovine PBMC more than four years after vaccination. This work contributes to our understanding of vaccine efficacy.

中文翻译：

牛主要组织相容性复合体Ⅱ类四聚体检测长效记忆口蹄疫（FMD）病毒血清O型特异性CD4+T细胞

口蹄疫 (FMD) 是偶蹄动物的一种高度传染性、经济上毁灭性的疾病。开发持久有效的口蹄疫疫苗将极大地有益于全球口蹄疫控制计划。由于缺乏特定物种的工具，对接种 FMD 疫苗的牛的适应性免疫进行深入分析在技术上具有挑战性。在这项研究中，我们旨在鉴定FMD 病毒 (FMDV) 衣壳中的CD4 ⁺ T 细胞表位，并使用牛主要组织相容性复合体 (BoLA) II 类四聚体对识别它们的 CD4 ⁺ T 细胞进行表型分析。基于DRA / DRB3*020 的BoLA II 类四聚体：02来自牛疫苗接种者的等位基因和 FMDV 抗原刺激的 PBMC 用于成功鉴定 FMDV 衣壳中的四个表位，其中三个以前没有报道过；在结构蛋白VP1中鉴定出两个表位，一个在VP3中，一个在VP4中。通过增殖测定证实了三个新表位的特异性。所有表位扩增的 T 细胞群都在体外产生 IFN-γ ，表明 FMD 疫苗接种后存在持久的 Th1 细胞表型。VP3 特异性 CD4 ⁺ T 细胞在已鉴定的表位中表现出最高频率，占 CD4 ⁺ T 细胞群的>0·004% 。CD45RO ⁺ CCR7 ⁺定义的中央存储器 CD4 ⁺T 细胞亚群在来自体外FMD 疫苗接种牛的FMDV 特异性 CD4 ⁺ T细胞群中以更高的频率存在。这表明在 FMD 疫苗接种后维持细胞适应性免疫的重要作用。值得注意的是，接种FMDV 表位的四聚体在接种疫苗 4 年后检测到牛 PBMC 中存在 FMDV 特异性 CD4 ⁺ T 细胞。这项工作有助于我们了解疫苗功效。

更新日期：2021-05-18

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