Peculiarities of the Presentation of the Encephalitogenic MBP Peptide by HLA-DR Complexes Providing Protection and Predisposition to Multiple Sclerosis
| Autor: | Ioanna N. Filimonova, A. E. Mamedov, Ivan V. Smirnov, Alexey A. Belogurov |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
musculoskeletal diseases Hemagglutinin (influenza) MBP peptide Peptide multiple sclerosis Biochemistry 03 medical and health sciences Myelin 0302 clinical medicine HLA-DR medicine Allele protective allele Gene Molecular Biology risk allele chemistry.chemical_classification biology Multiple sclerosis medicine.disease Myelin basic protein 030104 developmental biology medicine.anatomical_structure chemistry Immunology viral peptide biology.protein Molecular Medicine 030217 neurology & neurosurgery Biotechnology Research Article |
| Zdroj: | Acta Naturae |
| ISSN: | 2075-8251 |
| Popis: | Predisposition to multiple sclerosis (MS), a chronic autoimmune disease of the central nervous system, is due to various factors. The genetic component is considered one of the most important factors. HLA class II genes contribute the most to the development of MS. The HLA-DRB1*15 allele group is considered one of the main genetic risk factors predisposing to MS. The group of HLA-DRB1*01 alleles was shown to have a protective effect against this disease in the Russian population. In this work, we compared the binding of the encephalitogenic fragment of the myelin basic protein (MBP) to two HLA-DR complexes that provide protection against and predisposition to MS: HLA-DR1 (HLA-DRB1*0101) and HLA-DR15 (HLA-DRB1*1501), respectively. We found that the myelin peptide MBP88-100 binds to HLA-DR1 at a rate almost an order of magnitude lower than the viral peptide of hemagglutinin (HA). The same was true for the binding of MBP85-97 to HLA-DR15 in comparison with viral pp65. The structure of the C-terminal part of the peptide plays a key role in the binding to HLA-DR1 for equally high-affinity N-terminal regions of the peptides. The IC50 of the myelin peptide MBP88-100 competing with viral HA for binding to HLA-DR1 is almost an order of magnitude higher than that of HA. As for HA, the same was also true for the binding of MBP85-97 to HLA-DR15 in comparison with viral pp65. Thus, autoantigenic MBP cannot compete with the viral peptide for binding to protective HLA-DR1. However, it is more competitive than viral peptide for HLA-DR15. |
| Databáze: | OpenAIRE |
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