Crystal structures of H-2Db in complex with the LCMV-derived peptides GP92 and GP392 explain pleiotropic effects of glycosylation on antigen presentation and immunogenicity
| Autor: | I. Hafstrand, Adil Doganay Duru, Tatyana Sandalova, Adnane Achour, J. Buratto, Benjamin J. Josey, Sara Pellegrino, Daniel Badia-Martinez, Melissa Norström |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Glycosylation Physiology Glycobiology lcsh:Medicine CD8-Positive T-Lymphocytes Crystallography X-Ray Biochemistry Physical Chemistry Epitope chemistry.chemical_compound Epitopes Mice White Blood Cells Animal Cells Immune Physiology Medicine and Health Sciences Lymphocytic choriomeningitis virus Public and Occupational Health Post-Translational Modification Amino Acids lcsh:Science Antigens Viral Antigen Presentation Multidisciplinary Crystallography Immune System Proteins T Cells Organic Compounds Immunogenicity Physics Acidic Amino Acids Condensed Matter Physics Vaccination and Immunization Cell biology Chemistry Physical Sciences Crystal Structure Asparagine Cellular Types Research Article Immune Cells Antigen presentation Immunology Cytotoxic T cells chemical and pharmacologic phenomena Lymphocytic choriomeningitis 03 medical and health sciences Immune system Antigen medicine Animals Solid State Physics Antigens Blood Cells Chemical Bonding Organic Chemistry lcsh:R H-2 Antigens Chemical Compounds Biology and Life Sciences Proteins Hydrogen Bonding Cell Biology medicine.disease CTL 030104 developmental biology chemistry Solvents lcsh:Q Preventive Medicine Peptides Protein Processing Post-Translational T-Lymphocytes Cytotoxic |
| Zdroj: | PLoS ONE, Vol 12, Iss 12, p e0189584 (2017) PLoS ONE 'PloS One ', vol: 12, pages: e0189584-1-e0189584-17 (2017) |
| ISSN: | 1932-6203 |
| Popis: | Post-translational modifications significantly broaden the epitope repertoire for major histocompatibility class I complexes (MHC-I) and may allow viruses to escape immune recognition. Lymphocytic choriomeningitis virus (LCMV) infection of H-2b mice generates CD8+ CTL responses directed towards several MHC-I-restricted epitopes including the peptides GP92 (CSANNSHHYI) and GP392 (WLVTNGSYL), both with a N-glycosylation site. Interestingly, glycosylation has different effects on the immunogenicity and association capacity of these two epitopes to H-2Db. To assess the structural bases underlying these functional results, we determined the crystal structures of H-2Db in complex with GP92 (CSANNSHHYI) and GP392 (WLVTNGSYL) to 2.4 and 2.5 A resolution, respectively. The structures reveal that while glycosylation of GP392 most probably impairs binding, the glycosylation of the asparagine residue in GP92, which protrudes towards the solvent, possibly allows for immune escape and/or forms a neo-epitope that may select for a different set of CD8 T cells. Altogether, the presented results provide a structural platform underlying the effects of post-translational modifications on epitope binding and/or immunogenicity, resulting in viral immune escape. |
| Databáze: | OpenAIRE |
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