Fleming-Canepa Ximena, Jensen Shawna M, Mesa Christine M, Diaz-Satizabal Laura, Roth Alexa J, Parks-Dely Julie A, Moon Debra A, Wong Janet P, Evseev Danyel, Gossen Desolie A, Tetrault David G, Magor Katharine E
Department of Biological Sciences and the Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta T6G 2E9, Canada.
Department of Biological Sciences and the Li Ka Shing Institute of Virology, University of Alberta, Edmonton, Alberta T6G 2E9, Canada
J Immunol. 2016 Aug 1;197(3):783-94. doi: 10.4049/jimmunol.1502450. Epub 2016 Jun 24.
MHC class I is critically involved in defense against viruses, and diversity from polygeny and polymorphism contributes to the breadth of the immune response and health of the population. In this article, we examine MHC class I diversity in wild mallard ducks, the natural host and reservoir of influenza A viruses. We previously showed domestic ducks predominantly use UAA, one of five MHC class I genes, but whether biased expression is also true for wild mallards is unknown. Using RT-PCR from blood, we examined expressed MHC class I alleles from 38 wild mallards (Anas platyrhynchos) and identified 61 unique alleles, typically 1 or 2 expressed alleles in each individual. To determine whether expressed alleles correspond to UAA adjacent to TAP2 as in domestic ducks, we cloned and sequenced genomic UAA-TAP2 fragments from all mallards, which matched transcripts recovered and allowed us to assign most alleles as UAA Allelic differences are primarily located in α1 and α2 domains in the residues known to interact with peptide in mammalian MHC class I, suggesting the diversity is functional. Most UAA alleles have unique residues in the cleft predicting distinct specificity; however, six alleles have an unusual conserved cleft with two cysteine residues. Residues that influence peptide-loading properties and tapasin involvement in chicken are fixed in duck alleles and suggest tapasin independence. Biased expression of one MHC class I gene may make viral escape within an individual easy, but high diversity in the population places continual pressure on the virus in the reservoir species.
MHC I类分子在抵御病毒方面起着关键作用，其多基因性和多态性所产生的多样性有助于免疫反应的广度和种群的健康。在本文中，我们研究了野生绿头鸭（甲型流感病毒的天然宿主和储存宿主）的MHC I类分子多样性。我们之前发现家鸭主要使用五个MHC I类基因之一的UAA，但野生绿头鸭是否也存在偏向性表达尚不清楚。我们利用血液中的RT-PCR技术，检测了38只野生绿头鸭（绿头鸭）表达的MHC I类等位基因，共鉴定出61个独特的等位基因，每个个体通常表达1个或2个等位基因。为了确定表达的等位基因是否像在家鸭中那样对应于与TAP2相邻的UAA，我们克隆并测序了所有绿头鸭的基因组UAA-TAP2片段，这些片段与回收的转录本相匹配，使我们能够将大多数等位基因确定为UAA。等位基因差异主要位于与哺乳动物MHC I类分子中与肽相互作用的已知残基的α1和α2结构域，表明这种多样性具有功能性。大多数UAA等位基因在裂隙中具有独特的残基，预示着不同的特异性；然而，有六个等位基因具有异常保守的裂隙，带有两个半胱氨酸残基。影响鸡中肽装载特性和塔帕辛参与的残基在鸭等位基因中是固定的，这表明鸭对塔帕辛不依赖。一个MHC I类基因的偏向性表达可能使个体内的病毒逃逸变得容易，但种群中的高度多样性对储存宿主物种中的病毒持续施加压力。
