The canine MHC class Ia allele DLA-88*508:01 presents diverse self- and canine distemper virus-origin peptides of varying length that have a conserved binding motif.
The canine MHC class Ia allele DLA-88*508:01 presents diverse self- and canine distemper virus-origin peptides of varying length that have a conserved binding motif.
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DOI：
10.1016/j.vetimm.2018.01.005
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发表时间：
2018-03
影响因子：
1.8
通讯作者：
Hess PR
中科院分区：
文献类型：
--
作者：
Ross P;Nemec PS;Kapatos A;Miller KR;Holmes JC;Suter SE;Buntzman AS;Soderblom EJ;Collins EJ;Hess PR
理想情况下，CD8+ t细胞对病毒感染细胞或恶性细胞的反应是在特定肽和限制MHC I类元素的水平上确定的，这在狗身上尚未确定。为了推进犬CTL表位的发现，我们试图确定一个假定的经典MHC Ia类基因狗白细胞抗原(DLA)-88是否呈现来自病毒性病原体犬瘟热病毒（CDV）的肽。为了研究这种可能性，在金毛猎犬中普遍存在的等位基因DLA-88*508:01在犬组织细胞中以flag标记的结构体表达，以便对肽-DLA-88复合物进行亲和纯化，并随后洗脱结合肽。通过液相色谱-串联质谱（LC-MS/MS）测定的自肽序列模式分析，可以推断出结合偏好。DLA-88*508:01结合长度为9- 12个氨基酸的肽，对9-和11-mers有一定的偏好。疏水残基在第2和第3位，K、R或F残基在c端也是如此。使用DLA-88*508:01转染的tap缺陷RMA-S细胞系，通过多肽- mhc表面稳定实验测试基序匹配和不匹配的合成肽支持这些结论。采用LC-MS/MS技术，在CDV感染的DLA-88*508:01洗脱液中鉴定出22个长度为9 ~ 12个残基的病毒肽。结合基序分析和表面稳定实验数据表明，这22个多肽中有11个被加工并呈现，这些多肽来自CDV融合、血凝素、大聚合酶、基质、核衣壳、磷酸化蛋白和V蛋白，因此，它们是携带DLA-88*508:01的犬抗病毒CTL的潜在靶点。不同的自身和病毒肽的呈现表明，DLA-88是一个典型的MHC Ia类基因。
Ideally, CD8+ T-cell responses against virally infected or malignant cells are defined at the level of the specific peptide and restricting MHC class I element, a determination not yet made in the dog. To advance the discovery of canine CTL epitopes, we sought to determine whether a putative classical MHC class Ia gene, Dog Leukocyte Antigen (DLA)-88, presents peptides from a viral pathogen, canine distemper virus (CDV). To investigate this possibility, DLA-88*508:01, an allele prevalent in Golden Retrievers, was expressed as a FLAG-tagged construct in canine histiocytic cells to allow affinity purification of peptide-DLA-88 complexes and subsequent elution of bound peptides. Pattern analysis of self peptide sequences, which were determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS), permitted binding preferences to be inferred. DLA-88*508:01 binds peptides that are 9-to-12 amino acids in length, with a modest preference for 9- and 11-mers. Hydrophobic residues are favored at positions 2 and 3, as are K, R or F residues at the C-terminus. Testing motif-matched and -unmatched synthetic peptides via peptide-MHC surface stabilization assay using a DLA-88*508:01-transfected, TAP-deficient RMA-S line supported these conclusions. With CDV infection, 22 viral peptides ranging from 9-to-12 residues in length were identified in DLA-88*508:01 eluates by LC-MS/MS. Combined motif analysis and surface stabilization assay data suggested that 11 of these 22 peptides, derived from CDV fusion, hemagglutinin, large polymerase, matrix, nucleocapsid, phosphoprotein, and V proteins, were processed and presented, and thus, potential targets of anti-viral CTL in DLA-88*508:01-bearing dogs. The presentation of diverse self and viral peptides indicates that DLA-88 is a classical MHC class Ia gene.
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影响因子：
4.8
作者：
Hudrisier, D;Mazarguil, H;Gairin, JE
通讯作者：
Gairin, JE
影响因子：
3.7
作者：
Bund, D.;Buhmann, R.;Schmetzer, H. M.
通讯作者：
Schmetzer, H. M.
影响因子：
4.4
作者：
Hickman, HD;Luis, AD;Hildebrand, WH
通讯作者：
Hildebrand, WH
影响因子：
2.9
作者：
Batalia, MA;Kirksey, TJ;Collins, EJ
通讯作者：
Collins, EJ
影响因子：
4.3
作者：
Georges, GE;Lesnikova, M;Nash, RA
通讯作者：
Nash, RA