Chemical Modification of Influenza CD8+ T-Cell Epitopes Enhances Their Immunogenicity Regardless of Immunodominance
| العنوان: | Chemical Modification of Influenza CD8+ T-Cell Epitopes Enhances Their Immunogenicity Regardless of Immunodominance |
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| المؤلفون: | Ronald Jacobi, Kim Kapteijn, Josine van Beek, Rieuwert Hoppes, Jolien J. Luimstra, Marion Hendriks, Boris Rodenko, Casper Ouwerkerk, Sietske K. Rosendahl Huber, Jørgen de Jonge, Huib Ovaa |
| المصدر: | PLoS ONE, Vol 11, Iss 6, p e0156462 (2016) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2016. |
| سنة النشر: | 2016 |
| مصطلحات موضوعية: | 0301 basic medicine, Viral Diseases, Physiology, Epitopes, T-Lymphocyte, lcsh:Medicine, CD8-Positive T-Lymphocytes, HLA-A3 Antigen, Lymphocyte Activation, Biochemistry, Epitope, Major Histocompatibility Complex, White Blood Cells, 0302 clinical medicine, Animal Cells, Immune Physiology, Medicine and Health Sciences, Cytotoxic T cell, Public and Occupational Health, Amino Acids, lcsh:Science, Vaccines, Immune System Proteins, Multidisciplinary, T Cells, Organic Compounds, Immunogenicity, Vaccination, Flow Cytometry, Vaccination and Immunization, Chemistry, Infectious Diseases, medicine.anatomical_structure, Physical Sciences, Cellular Types, Research Article, Protein Binding, Immune Cells, T cell, Immunology, Cytotoxic T cells, Fluorescence Polarization, Mice, Transgenic, Immunodominance, Biology, Major histocompatibility complex, 03 medical and health sciences, Orthomyxoviridae Infections, Antigen, HLA-A2 Antigen, Influenza, Human, MHC class I, medicine, Animals, Humans, Amino Acid Sequence, Antigens, Blood Cells, Immunodominant Epitopes, Organic Chemistry, lcsh:R, Chemical Compounds, Biology and Life Sciences, Proteins, Cell Biology, Virology, Influenza, 030104 developmental biology, Amino Acid Substitution, biology.protein, Clinical Immunology, lcsh:Q, Preventive Medicine, Clinical Medicine, Peptides, 030215 immunology |
| الوصف: | T cells are essential players in the defense against infection. By targeting the MHC class I antigen-presenting pathway with peptide-based vaccines, antigen-specific T cells can be induced. However, low immunogenicity of peptides poses a challenge. Here, we set out to increase immunogenicity of influenza-specific CD8+ T cell epitopes. By substituting amino acids in wild type sequences with non-proteogenic amino acids, affinity for MHC can be increased, which may ultimately enhance cytotoxic CD8+ T cell responses. Since preventive vaccines against viruses should induce a broad immune response, we used this method to optimize influenza-specific epitopes of varying dominance. For this purpose, HLA-A*0201 epitopes GILGFVFTL, FMYSDFHFI and NMLSTVLGV were selected in order of decreasing MHC-affinity and dominance. For all epitopes, we designed chemically enhanced altered peptide ligands (CPLs) that exhibited greater binding affinity than their WT counterparts; even binding scores of the high affinity GILGFVFTL epitope could be improved. When HLA-A*0201 transgenic mice were vaccinated with selected CPLs, at least 2 out of 4 CPLs of each epitope showed an increase in IFN-γ responses of splenocytes. Moreover, modification of the low affinity epitope NMLSTVLGV led to an increase in the number of mice that responded. By optimizing three additional influenza epitopes specific for HLA-A*0301, we show that this strategy can be extended to other alleles. Thus, enhancing binding affinity of peptides provides a valuable tool to improve the immunogenicity and range of preventive T cell-targeted peptide vaccines. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b19dc21958b6104da8b7c0db1c21c663Test http://europepmc.org/articles/PMC4917206?pdf=renderTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b19dc21958b6104da8b7c0db1c21c663 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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