Breadth of the CD4+ T cell response to Anaplasma marginale VirB9-1, VirB9-2 and VirB10 and MHC class II DR and DQ restriction elements.
Breadth of the CD4+ T cell response to Anaplasma marginale VirB9-1, VirB9-2 and VirB10 and MHC class II DR and DQ restriction elements.
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DOI：
10.1007/s00251-012-0606-4
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发表时间：
2012-07
期刊：
影响因子：
3.2
通讯作者：
Brown, Wendy C.
中科院分区：
文献类型：
--
作者：
Morse, Kaitlyn;Norimine, Junzo;Hope, Jayne C.;Brown, Wendy C.
关键词：
MHC II类分子影响由免疫和感染引发的抗原特异性CD 4 + T淋巴细胞应答。CD 4 + T细胞应答对于控制包括边缘无浆体在内的许多细菌病原体的感染是重要的，并且在用保护性A.边缘外膜（OM）疫苗。构成保护性OM疫苗的免疫原性蛋白包括IV型分泌系统（T4 SS）蛋白VirB 9 -1、VirB 9 -2和VirB 10，它们是包含在多表位疫苗中的候选物。我们的目标是确定VirB 9 -1，VirB 9 -2和VirB 10 T细胞反应和MHC II类限制性元件的宽度在6头牛与不同的MHC II类单倍型，定义为DRB 3，DQA和DQB等位基因组合的每只动物。在T细胞增殖测定中，用自体抗原呈递细胞（APC）和表达牛DR和DQ分子的组合的人工APC测试跨越每种T4 SS蛋白的重叠肽。鉴定了二十种免疫刺激肽;三种代表VirB 9 -1中的两个或更多个表位，十种代表VirB 9 -2中的八个或更多个表位，七种代表VirB 10中的七个或更多个表位。在8个DRB 3分子中，4个分子呈现15个肽，这是偏倚的，因为DRB 3/DRB 3 *1201呈现10个肽，而DRB 3/DRB 3 *1101呈现4个肽。由2个单倍型内和2个单倍型间对组成的4个DQA/DQB分子共呈递7个肽段，其中5个肽段为DQ分子所独有。此外，还鉴定了三种功能性混合同种型（DQA/DRB 3）限制性元件。多个VirB 9 -1、VirB 9 -2和VirB 10肽表位的免疫原性和广泛的MHC II类呈递证明了它们作为抗A.边缘。
MHC class II molecules influence antigen-specific CD4+ T-lymphocyte responses primed by immunization and infection. CD4+ T-cell responses are important for controlling infection by many bacterial pathogens including Anaplasma marginale, and are observed in cattle immunized with the protective A. marginale outer membrane (OM) vaccine. Immunogenic proteins that comprise the protective OM vaccine include type IV secretion system (T4SS) proteins VirB9-1, VirB9-2, and VirB10, candidates for inclusion in a multi-epitope vaccine. Our goal was to determine the breadth of the VirB9-1, VirB9-2, and VirB10 T-cell response and MHC class II restriction elements in six cattle with different MHC class II haplotypes, defined by DRB3, DQA, and DQB allele combinations for each animal. Overlapping peptides spanning each T4SS protein were tested in T-cell proliferation assays with autologous antigen presenting cells (APC) and artificial APC expressing combinations of bovine DR and DQ molecules. Twenty immunostimulatory peptides were identified; three representing two or more epitopes in VirB9-1, ten representing eight or more epitopes in VirB9-2, and seven representing seven or more epitopes in VirB10. Of eight DRA/DRB3 molecules, four presented 15 peptides, which was biased as DRA/DRB3*1201 presented ten and DRA/DRB3*1101 presented four peptides. Four DQA/DQB molecules composed of two intrahaplotype and two interhaplotype pairs presented seven peptides, of which five were uniquely presented by DQ molecules. In addition,three functional mixed isotype (DQA/DRB3) restriction elements were identified. The immunogenicity and broad MHC class II presentation of multiple VirB9-1, VirB9-2, and VirB10 peptide epitopes justify their testing as a multi-epitope vaccine against A. marginale.
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影响因子：
3.1
作者：
Lopez, JE;Siems, WF;Brown, WC
通讯作者：
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影响因子：
4.4
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