Identification of Cytotoxic T Lymphocyte Epitopes on Swine Viruses: Multi-Epitope Design for Universal T Cell Vaccine

Liao, Yu-Chieh; Lin, Hsin-Hung; Lin, Chih-Long; Chung, Wen-Bin

doi:10.1371/journal.pone.0084443

Cited by 22 publications

(16 citation statements)

References 33 publications

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“…In chronic viral infections, the regulatory element Ppp2r2d plays a significant role in CTL dysfunction [128]. Other in vivo studies have not tested for the predicted PRRSV epitopes that would induce CTL responses [129] and have used nonswine animal models. This complicates interpretation of the small literature available on this subject.…”

Section: The Cytotoxic T Lymphocyte Response To Prrsvmentioning

confidence: 99%

Porcine reproductive and respiratory syndrome (PRRS): an immune dysregulatory pandemic

et al. 2014

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Porcine reproductive and respiratory disease syndrome (PRRS) is a viral pandemic that especially affects neonates within the "critical window" of immunological development. PRRS was recognized in 1987 and within a few years became pandemic causing an estimated yearly $600,000 economic loss in the USA with comparative losses in most other countries. The causative agent is a single-stranded, positive-sense enveloped arterivirus (PRRSV) that infects macrophages and plasmacytoid dendritic cells. Despite the discovery of PRRSV in 1991 and the publication of >2,000 articles, the control of PRRS is problematic. Despite the large volume of literature on this disease, the cellular and molecular mechanisms describing how PRRSV dysregulates the host immune system are poorly understood. We know that PRRSV suppresses innate immunity and causes abnormal B cell proliferation and repertoire development, often lymphopenia and thymic atrophy. The PRRSV genome is highly diverse, rapidly evolving but amenable to the generation of many mutants and chimeric viruses for experimental studies. PRRSV only replicates in swine which adds to the experimental difficulty since no inbred well-defined animal models are available. In this article, we summarize current knowledge and apply it toward developing a series of provocative and testable hypotheses to explain how PRRSV immunomodulates the porcine immune system with the goal of adding new perspectives on this disease.

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Section: The Cytotoxic T Lymphocyte Response To Prrsvmentioning

confidence: 99%

Porcine reproductive and respiratory syndrome (PRRS): an immune dysregulatory pandemic

et al. 2014

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“…CTL epitopes might be a requirement of optimal PRRSV immunity for the control and treatment of PRRSV infection (36,37). In our study, a novel approach was used to select PRRSV CTL epitopes, i.e., starting from a computer prediction for PRRSV peptides, followed by in vitro complex refolding with SLA-1 * 1502, the analysis of the complex crystal structure, the identification of SLA-1 * 1502-restricted potential epitopes from whole genomes of different PRRSV strains, and finally, verification of the immunogenicity of SLA-1 * 1502-restricted PRRSV epitope.…”

Section: Discussionmentioning

confidence: 99%

Illumination of PRRSV Cytotoxic T Lymphocyte Epitopes by the Three-Dimensional Structure and Peptidome of Swine Lymphocyte Antigen Class I (SLA-I)

et al. 2020

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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.

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“…Without this information many more alleles than actually necessary might have to be covered. Performing predictions for all known alleles is only practical for screening a small number of known antigens or perhaps scanning a viral genome for epitopes ( Liao et al , 2013 ). The alternative is to make a best guess of the target alleles and select for promiscuity, as pursued here.…”

Section: Discussionmentioning

confidence: 99%

Integrated computational prediction and experimental validation identifies promiscuous T cell epitopes in the proteome of Mycobacterium bovis

et al. 2016

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The discovery of novel antigens is an essential requirement in devising new diagnostics or vaccines for use in control programmes against human tuberculosis (TB) and bovine tuberculosis (bTB). Identification of potential epitopes recognised by CD4+ T cells requires prediction of peptide binding to MHC class-II, an obligatory prerequisite for T cell recognition. To comprehensively prioritise potential MHC-II-binding epitopes from Mycobacterium bovis, the agent of bTB and zoonotic TB in humans, we integrated three binding prediction methods with the M. bovisproteome using a subset of human HLA alleles to approximate the binding of epitope-containing peptides to the bovine MHC class II molecule BoLA-DRB3. Two parallel strategies were then applied to filter the resulting set of binders: identification of the top-scoring binders or clusters of binders. Our approach was tested experimentally by assessing the capacity of predicted promiscuous peptides to drive interferon-γ secretion from T cells of M. bovis infected cattle. Thus, 376 20-mer peptides, were synthesised (270 predicted epitopes, 94 random peptides with low predictive scores and 12 positive controls of known epitopes). The results of this validation demonstrated significant enrichment (>24 %) of promiscuously recognised peptides predicted in our selection strategies, compared with randomly selected peptides with low prediction scores. Our strategy offers a general approach to the identification of promiscuous epitopes tailored to target populations where there is limited knowledge of MHC allelic diversity.

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Identification of Cytotoxic T Lymphocyte Epitopes on Swine Viruses: Multi-Epitope Design for Universal T Cell Vaccine

Cited by 22 publications

References 33 publications

Porcine reproductive and respiratory syndrome (PRRS): an immune dysregulatory pandemic

Porcine reproductive and respiratory syndrome (PRRS): an immune dysregulatory pandemic

Illumination of PRRSV Cytotoxic T Lymphocyte Epitopes by the Three-Dimensional Structure and Peptidome of Swine Lymphocyte Antigen Class I (SLA-I)

Integrated computational prediction and experimental validation identifies promiscuous T cell epitopes in the proteome of Mycobacterium bovis

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