Sequence diversity between class I MHC loci of African native and introduced Bos taurus cattle in Theileria parva endemic regions: in silico peptide binding prediction identifies distinct functional clusters
Sequence diversity between class I MHC loci of African native and introduced Bos taurus cattle in Theileria parva endemic regions: in silico peptide binding prediction identifies distinct functional clusters
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DOI：
10.1007/s00251-016-0902-5
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发表时间：
2016-05-01
期刊：
影响因子：
3.2
通讯作者：
Bishop, Richard P.
中科院分区：
文献类型：
--
作者：
Obara, Isaiah;Nielsen, Morten;Bishop, Richard P.
有强有力的证据表明，用于控制原生动物寄生虫小泰勒虫的活疫苗接种诱导的免疫力是由针对感染牛淋巴细胞的寄生虫的前体阶段的I类MHC限制性CD8（+）T细胞介导的。I类MHC基因的功能能力依赖于指定排列在肽结合沟中的某些关键氨基酸残基的密码子的存在。与欧洲普通牛I类MHC等位基因多态性已被广泛研究的情况相比，发表的非洲牛T.细小病毒流行区非常有限。我们利用454焦磷酸测序的多重功能，在Ankole牛群体中对I类MHC等位基因多样性进行初步评估。我们还分型人口的外来荷斯坦牛从非洲牧场的I类MHC和调查的程度，如果有的话，他们的肽结合基序与Ankole牛重叠。我们报告了18个新的等位基因序列在Ankole牛的鉴定和序列多样性，包括在残基主要与肽相互作用的积极选择提供的证据。在电脑功能分析导致肽结合特异性，这在很大程度上是不同的两个品种。我们还证明了来自T. parva不识别最初在Holstein和Boran（Bos indicus）牛品种中鉴定的疫苗候选抗原。
There is strong evidence that the immunity induced by live vaccination for control of the protozoan parasite Theileria parva is mediated by class I MHC-restricted CD8(+) T cells directed against the schizont stage of the parasite that infects bovine lymphocytes. The functional competency of class I MHC genes is dependent on the presence of codons specifying certain critical amino acid residues that line the peptide binding groove. Compared with European Bos taurus in which class I MHC allelic polymorphisms have been examined extensively, published data on class I MHC transcripts in African taurines in T. parva endemic areas is very limited. We utilized the multiplexing capabilities of 454 pyrosequencing to make an initial assessment of class I MHC allelic diversity in a population of Ankole cattle. We also typed a population of exotic Holstein cattle from an African ranch for class I MHC and investigated the extent, if any, that their peptide-binding motifs overlapped with those of Ankole cattle. We report the identification of 18 novel allelic sequences in Ankole cattle and provide evidence of positive selection for sequence diversity, including in residues that predominantly interact with peptides. In silico functional analysis resulted in peptide binding specificities that were largely distinct between the two breeds. We also demonstrate that CD8(+) T cells derived from Ankole cattle that are seropositive for T. parva do not recognize vaccine candidate antigens originally identified in Holstein and Boran (Bos indicus) cattle breeds.