Polymorphisms and tissue expression of the feline leukocyte antigen class I loci FLAI-E, FLAI-H, and FLAI-K.
Polymorphisms and tissue expression of the feline leukocyte antigen class I loci FLAI-E, FLAI-H, and FLAI-K.
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DOI：
10.1007/s00251-013-0711-z
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发表时间：
2013-09
期刊：
影响因子：
3.2
通讯作者：
Hess, Paul R.
中科院分区：
文献类型：
--
作者：
Holmes, Jennifer C.;Holmer, Savannah G.;Ross, Peter;Buntzman, Adam S.;Frelinger, Jeffrey A.;Hess, Paul R.
细胞内病原体（如病毒）的细胞毒性CD 8 + T细胞免疫监视由经典的主要组织相容性复合体（MHC）Ia类分子控制，并且理想地，这些抗病毒T细胞群体由特异性肽和限制性MHC等位基因限定。令人惊讶的是，尽管猫在模拟人类病毒免疫中的效用，但对猫白细胞抗原I类复合物（FLAI）知之甚少。只有少数的编码序列与不确定的基因座起源和表达模式已被报道。在19个I类基因中，3个位点- FLAI-E，-H和-K -被预测为编码经典分子，我们的目标是通过分析多态性和组织表达来评估它们的状态。使用位点特异性，PCR为基础的基因分型，我们扩增33 FLAI-E，-H，和-K等位基因从12只猫的不同品种，确定，第一次，在3个不同的基因座在猫科动物的等位基因。等位基因在α1/α2结构域中具有预期的多态性和不变位点，全长cDNA克隆具有所有特征性Ia类外显子。等位基因可以分配到一个特定的基因座与合理的信心，虽然有证据表明潜在的混淆基因间重组FLAI-E和-K。从多种组织类型的cDNA中仅扩增出FLAI-E、-H和-K起源的等位基因。我们还定义了这些基因的高变区，这使得新的和已建立的等位基因都可以命名。正如预测的那样，FLAI-E、-H和-K满足Ia类基因的主要标准。这些数据是研究猫表位特异性抗病毒CD 8 + T细胞应答的必要前提。
Cytotoxic CD8+ T-cell immunosurveillance for intracellular pathogens, such as viruses, is controlled by classical major histocompatibility complex (MHC) class Ia molecules, and ideally, these antiviral T-cell populations are defined by the specific peptide and restricting MHC allele. Surprisingly, despite the utility of the cat in modeling human viral immunity, little is known about the Feline Leukocyte Antigen class I complex (FLAI). Only a few coding sequences with uncertain locus origin and expression patterns have been reported. Of 19 class I genes, 3 loci - FLAI-E, -H and -K – are predicted to encode classical molecules, and our objective was to evaluate their status by analyzing polymorphisms and tissue expression. Using locus-specific, PCR-based genotyping, we amplified 33 FLAI-E, -H, and -K alleles from 12 cats of various breeds, identifying, for the first time, alleles across 3 distinct loci in a feline species. Alleles shared the expected polymorphic and invariant sites in the α1/α2 domains, and full-length cDNA clones possessed all characteristic class Ia exons. Alleles could be assigned to a specific locus with reasonable confidence, although there was evidence of potentially confounding interlocus recombination between FLAI-E and -K. Only FLAI-E, -H and -K-origin alleles were amplified from cDNAs of multiple tissue types. We also defined hypervariable regions across these genes, which permitted the assignment of names to both novel and established alleles. As predicted, FLAI-E, -H, and -K fulfill the major criteria of class Ia genes. These data represent a necessary prerequisite for studying epitope-specific antiviral CD8+ T-cell responses in cats.
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