Crystal Structure of Swine Major Histocompatibility Complex Class I SLA-1*0401 and Identification of 2009 Pandemic Swine-Origin Influenza A H1N1 Virus Cytotoxic T Lymphocyte Epitope Peptides
Crystal Structure of Swine Major Histocompatibility Complex Class I SLA-1*0401 and Identification of 2009 Pandemic Swine-Origin Influenza A H1N1 Virus Cytotoxic T Lymphocyte Epitope Peptides
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DOI：
10.1128/jvi.05040-11
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发表时间：
2011-09
影响因子：
5.4
通讯作者：
Nianzhi Zhang;J. Qi;Sijia Feng;F. Gao;Jun Liu;X. Pan;Rong Chen;Qirun Li;Zhaosan Chen;
中科院分区：
文献类型：
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作者：
Nianzhi Zhang;J. Qi;Sijia Feng;F. Gao;Jun Liu;X. Pan;Rong Chen;Qirun Li;Zhaosan Chen;
猪白细胞抗原Ⅰ类（SLA Ⅰ）将病毒抗原表位呈递给细胞毒性T淋巴细胞（CTL）是猪免疫的关键。为了说明猪CTL表位呈递的结构基础，在本研究中确定了与源自2009年大流行H1N1（pH 1 N1）猪源甲型流感病毒（S-OIVNW 9; NSDTVGWSW）或埃博拉病毒（EbolaAY 9; ATAAATEAY）的肽复合的第一SLA晶体结构SLA-1*0401。正如预期的那样，肽-SLA-1*0401的整体结构类似于其他结构解析的肽主要组织相容性复合物（pMHC）的一般构象。SLA-1*0401的主要区别在于Arg 156由于其柔性侧链而在肽结合中具有“一票否决”功能。S-OIVNW 9和EbolaAY 9以相似的构象结合SLA-1*0401，但使用不同的水分子来稳定它们的结合。两种肽中P7残基的侧链暴露，表明表位是由该SLA呈递的“特征”肽。进一步的分析表明，SLA-1*0401和人类白细胞抗原（HLA）I类HLA-A*0101可以呈递相同的肽，但构象不同，表明跨物种表位呈递。采用体外复性方法筛选并评价了2009年大流行S-OIV的CTL表位肽。三个肽被鉴定为潜在的跨种流感病毒（IV）CTL表位。提出了SLA-1*0401的结合基序，并利用圆二色谱分析了关键肽-SLA-1*0401复合物的热稳定性。本研究结果不仅为SLA Ⅰ提呈多肽提供了结构基础，而且还鉴定了部分IV型CTL表位肽。这些结果将有利于疫苗开发和猪器官为基础的异种移植。
ABSTRACT The presentation of viral epitopes to cytotoxic T lymphocytes (CTLs) by swine leukocyte antigen class I (SLA I) is crucial for swine immunity. To illustrate the structural basis of swine CTL epitope presentation, the first SLA crystal structures, SLA-1*0401, complexed with peptides derived from either 2009 pandemic H1N1 (pH1N1) swine-origin influenza A virus (S-OIVNW9; NSDTVGWSW) or Ebola virus (EbolaAY9; ATAAATEAY) were determined in this study. The overall peptide–SLA-1*0401 structures resemble, as expected, the general conformations of other structure-solved peptide major histocompatibility complexes (pMHC). The major distinction of SLA-1*0401 is that Arg156 has a “one-ballot veto” function in peptide binding, due to its flexible side chain. S-OIVNW9 and EbolaAY9 bind SLA-1*0401 with similar conformations but employ different water molecules to stabilize their binding. The side chain of P7 residues in both peptides is exposed, indicating that the epitopes are “featured” peptides presented by this SLA. Further analyses showed that SLA-1*0401 and human leukocyte antigen (HLA) class I HLA-A*0101 can present the same peptides, but in different conformations, demonstrating cross-species epitope presentation. CTL epitope peptides derived from 2009 pandemic S-OIV were screened and evaluated by the in vitro refolding method. Three peptides were identified as potential cross-species influenza virus (IV) CTL epitopes. The binding motif of SLA-1*0401 was proposed, and thermostabilities of key peptide–SLA-1*0401 complexes were analyzed by circular dichroism spectra. Our results not only provide the structural basis of peptide presentation by SLA I but also identify some IV CTL epitope peptides. These results will benefit both vaccine development and swine organ-based xenotransplantation.