Illumination of PRRSV Cytotoxic T Lymphocyte Epitopes by the Three-Dimensional Structure and Peptidome of Swine Lymphocyte Antigen Class I (SLA-I)
To investigate CTL epitope applications in swine, SLA-1*1502-restricted peptide epitopes matching porcine reproductive and respiratory syndrome virus (PRRSV) strains were explored by crystallography, biochemistry, and the specific pathogen-free (SPF) swine experiments. First, nine predicted PRRSV pe...
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| Format: | Article |
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Frontiers Media S.A.
2020-01-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02995/full |
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| author | Xiaocheng Pan Xiaocheng Pan Nianzhi Zhang Xiaohui Wei Yinan Jiang Rong Chen Qirun Li Ruiying Liang Lijie Zhang Lizhen Ma Chun Xia Chun Xia |
| author_facet | Xiaocheng Pan Xiaocheng Pan Nianzhi Zhang Xiaohui Wei Yinan Jiang Rong Chen Qirun Li Ruiying Liang Lijie Zhang Lizhen Ma Chun Xia Chun Xia |
| author_sort | Xiaocheng Pan |
| collection | DOAJ |
| description | To investigate CTL epitope applications in swine, SLA-1*1502-restricted peptide epitopes matching porcine reproductive and respiratory syndrome virus (PRRSV) strains were explored by crystallography, biochemistry, and the specific pathogen-free (SPF) swine experiments. First, nine predicted PRRSV peptides were tested by assembly of the peptide-SLA-1*1502 (pSLA-1*1502) complexes, and the crystal structure of the SLA-1*1502 complex with one peptide (NSP9-TMP9) was determined. The NSP9-TMP9 peptide conformation presented by pSLA-1*1502 is different from that of the peptides presented by the known pSLA-1*0401 and pSLA-3*hs0202 complexes. Two consecutive Pro residues make the turn between P3 and P4 of NSP9-TMP9 much sharper. The D pocket of pSLA-1*1502 is unique and is important for peptide binding. Next, the potential SLA-1*1502-restricted peptide epitopes matching four typical genetic PRRSV strains were identified based on the peptide-binding motif of SLA-1*1502 determined by structural analysis and alanine scanning of the NSP9-TMP9 peptide. The tetrameric complex of SLA-1*1502 and NSP9-TMP9 was constructed and examined. Finally, taking NSP9-TMP9 as an example, the CTL immunogenicity of the identified PRRSV peptide epitope was evaluated. The SPF swine expressing the SLA-1*1502 alleles were divided into three groups: modified live vaccine (MLV), MLV+NSP9-TMP9, and the blank control group. NSP9-TMP9 was determined as a PRRSV CTL epitope with strong immunogenicity by flow cytometry and IFN-γ expression. Our study developed an integrated approach to identify SLA-I-restricted CTL epitopes from various important viruses and is helpful in designing and applying effective peptide-based vaccines for swine. |
| first_indexed | 2024-12-11T00:14:04Z |
| format | Article |
| id | doaj.art-07a9bd3cdf974c208b85061ff6c940fb |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-11T00:14:04Z |
| publishDate | 2020-01-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Immunology |
| spelling | doaj.art-07a9bd3cdf974c208b85061ff6c940fb2022-12-22T01:28:01ZengFrontiers Media S.A.Frontiers in Immunology1664-32242020-01-011010.3389/fimmu.2019.02995442174Illumination of PRRSV Cytotoxic T Lymphocyte Epitopes by the Three-Dimensional Structure and Peptidome of Swine Lymphocyte Antigen Class I (SLA-I)Xiaocheng Pan0Xiaocheng Pan1Nianzhi Zhang2Xiaohui Wei3Yinan Jiang4Rong Chen5Qirun Li6Ruiying Liang7Lijie Zhang8Lizhen Ma9Chun Xia10Chun Xia11Department of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaInstitute of Animal Husbandry and Veterinary Science, Anhui Academy of Agricultural Science, Hefei, ChinaDepartment of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaDepartment of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaDepartment of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaDepartment of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaDepartment of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaDepartment of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaDepartment of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaDepartment of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaDepartment of Microbiology and Immunology, College of Veterinary Medicine, China Agricultural University, Beijing, ChinaKey Laboratory of Animal Epidemiology of the Ministry of Agriculture, China Agricultural University, Beijing, ChinaTo investigate CTL epitope applications in swine, SLA-1*1502-restricted peptide epitopes matching porcine reproductive and respiratory syndrome virus (PRRSV) strains were explored by crystallography, biochemistry, and the specific pathogen-free (SPF) swine experiments. First, nine predicted PRRSV peptides were tested by assembly of the peptide-SLA-1*1502 (pSLA-1*1502) complexes, and the crystal structure of the SLA-1*1502 complex with one peptide (NSP9-TMP9) was determined. The NSP9-TMP9 peptide conformation presented by pSLA-1*1502 is different from that of the peptides presented by the known pSLA-1*0401 and pSLA-3*hs0202 complexes. Two consecutive Pro residues make the turn between P3 and P4 of NSP9-TMP9 much sharper. The D pocket of pSLA-1*1502 is unique and is important for peptide binding. Next, the potential SLA-1*1502-restricted peptide epitopes matching four typical genetic PRRSV strains were identified based on the peptide-binding motif of SLA-1*1502 determined by structural analysis and alanine scanning of the NSP9-TMP9 peptide. The tetrameric complex of SLA-1*1502 and NSP9-TMP9 was constructed and examined. Finally, taking NSP9-TMP9 as an example, the CTL immunogenicity of the identified PRRSV peptide epitope was evaluated. The SPF swine expressing the SLA-1*1502 alleles were divided into three groups: modified live vaccine (MLV), MLV+NSP9-TMP9, and the blank control group. NSP9-TMP9 was determined as a PRRSV CTL epitope with strong immunogenicity by flow cytometry and IFN-γ expression. Our study developed an integrated approach to identify SLA-I-restricted CTL epitopes from various important viruses and is helpful in designing and applying effective peptide-based vaccines for swine.https://www.frontiersin.org/article/10.3389/fimmu.2019.02995/fullSLAstructureCTLepitopePRRSVvaccine |
| spellingShingle | Xiaocheng Pan Xiaocheng Pan Nianzhi Zhang Xiaohui Wei Yinan Jiang Rong Chen Qirun Li Ruiying Liang Lijie Zhang Lizhen Ma Chun Xia Chun Xia Illumination of PRRSV Cytotoxic T Lymphocyte Epitopes by the Three-Dimensional Structure and Peptidome of Swine Lymphocyte Antigen Class I (SLA-I) Frontiers in Immunology SLA structure CTL epitope PRRSV vaccine |
| title | Illumination of PRRSV Cytotoxic T Lymphocyte Epitopes by the Three-Dimensional Structure and Peptidome of Swine Lymphocyte Antigen Class I (SLA-I) |
| title_full | Illumination of PRRSV Cytotoxic T Lymphocyte Epitopes by the Three-Dimensional Structure and Peptidome of Swine Lymphocyte Antigen Class I (SLA-I) |
| title_fullStr | Illumination of PRRSV Cytotoxic T Lymphocyte Epitopes by the Three-Dimensional Structure and Peptidome of Swine Lymphocyte Antigen Class I (SLA-I) |
| title_full_unstemmed | Illumination of PRRSV Cytotoxic T Lymphocyte Epitopes by the Three-Dimensional Structure and Peptidome of Swine Lymphocyte Antigen Class I (SLA-I) |
| title_short | Illumination of PRRSV Cytotoxic T Lymphocyte Epitopes by the Three-Dimensional Structure and Peptidome of Swine Lymphocyte Antigen Class I (SLA-I) |
| title_sort | illumination of prrsv cytotoxic t lymphocyte epitopes by the three dimensional structure and peptidome of swine lymphocyte antigen class i sla i |
| topic | SLA structure CTL epitope PRRSV vaccine |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02995/full |
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