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<article article-type="research-article" dtd-version="1.3" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xml:lang="ru"><front><journal-meta><journal-id journal-id-type="publisher-id">dan</journal-id><journal-title-group><journal-title xml:lang="ru">Доклады Национальной академии наук Беларуси</journal-title><trans-title-group xml:lang="en"><trans-title>Doklady of the National Academy of Sciences of Belarus</trans-title></trans-title-group></journal-title-group><issn pub-type="ppub">1561-8323</issn><issn pub-type="epub">2524-2431</issn><publisher><publisher-name>The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.29235/1561-8323-2024-68-4-325-334</article-id><article-id custom-type="elpub" pub-id-type="custom">dan-1207</article-id><article-categories><subj-group subj-group-type="heading"><subject>Research Article</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="ru"><subject>БИОЛОГИЯ</subject></subj-group><subj-group subj-group-type="section-heading" xml:lang="en"><subject>BIOLOGY</subject></subj-group></article-categories><title-group><article-title>Генетическая вариабельность главного аллергена пыльцы березы Bet v 1 и характеристика В- и Т-клеточных эпитопов</article-title><trans-title-group xml:lang="en"><trans-title>Genetic variability of the major birch pollen allergen Bet v 1 and characterization of B- and T-cell epitopes</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3984-393X</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Пархомчук</surname><given-names>О. Ю.</given-names></name><name name-style="western" xml:lang="en"><surname>Parkhomchuk</surname><given-names>O. Yu.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Пархомчук Ольга Юрьевна – науч. сотрудник, аспирант</p><p>ул. Фи лимонова, 23, 220114, Минск</p></bio><bio xml:lang="en"><p>Parkhomchuk Olga Yu. – Researcher, Postgraduate Student</p><p>23, Filimonov Str., 220114, Minsk</p></bio><email xlink:type="simple">olgaparhom4uk@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3028-1176</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Фомина</surname><given-names>Е. Г.</given-names></name><name name-style="western" xml:lang="en"><surname>Fomina</surname><given-names>E. G.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Фомина Елена Георгиевна – д-р биол. наук, заведующий лабораторией</p><p>ул. Филимонова, 23, 220114, Минск</p></bio><bio xml:lang="en"><p>Fomina Elena G. – D. Sc. (Biology), Head of the Laboratory</p><p>23, Filimonov Str., 220114, Minsk</p></bio><email xlink:type="simple">feg1@tut.by</email><xref ref-type="aff" rid="aff-2"/></contrib><contrib contrib-type="author" corresp="yes"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-3919-0625</contrib-id><name-alternatives><name name-style="eastern" xml:lang="ru"><surname>Григорьева</surname><given-names>Е. Е.</given-names></name><name name-style="western" xml:lang="en"><surname>Grigorieva</surname><given-names>E. E.</given-names></name></name-alternatives><bio xml:lang="ru"><p>Григорьева Елена Евгеньевна – канд. биол. наук, вед. науч. сотрудник, доцент</p><p>ул. Филимонова, 23, 220114, Минск</p></bio><bio xml:lang="en"><p>Grigorieva Elena E. – Ph. D. (Biology), Leading Researcher</p><p>23, Filimonov Str., 220114, Minsk</p></bio><email xlink:type="simple">grigus@mail.ru</email><xref ref-type="aff" rid="aff-1"/></contrib></contrib-group><aff-alternatives id="aff-1"><aff xml:lang="ru"><institution>РНПЦ эпидемиологии и микробиологии</institution></aff><aff xml:lang="en"><institution>Republican Scientific and Practical Center of Epidemiology and Microbiology</institution></aff></aff-alternatives><aff-alternatives id="aff-2"><aff xml:lang="ru"><institution>РНПЦ эпидемиологии и мик робиологии</institution></aff><aff xml:lang="en"><institution>Republican Scientific and Practical Center of Epidemiology and Microbiology</institution></aff></aff-alternatives><pub-date pub-type="collection"><year>2024</year></pub-date><pub-date pub-type="epub"><day>06</day><month>09</month><year>2024</year></pub-date><volume>68</volume><issue>4</issue><fpage>325</fpage><lpage>334</lpage><permissions><copyright-statement>Copyright &amp;#x00A9; Пархомчук О.Ю., Фомина Е.Г., Григорьева Е.Е., 2024</copyright-statement><copyright-year>2024</copyright-year><copyright-holder xml:lang="ru">Пархомчук О.Ю., Фомина Е.Г., Григорьева Е.Е.</copyright-holder><copyright-holder xml:lang="en">Parkhomchuk O.Y., Fomina E.G., Grigorieva E.E.</copyright-holder><license xml:lang="ru" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>Данная работа распространяется под лицензией Creative Commons Attribution 4.0.</license-p></license><license xml:lang="en" license-type="creative-commons-attribution" xlink:href="https://creativecommons.org/licenses/by/4.0/" xlink:type="simple"><license-p>This work is licensed under a Creative Commons Attribution 4.0 License.</license-p></license></permissions><self-uri xlink:href="https://doklady.belnauka.by/jour/article/view/1207">https://doklady.belnauka.by/jour/article/view/1207</self-uri><abstract><p>Исследована пыльца березы повислой, собранная в период апрель–май 2020, 2021 гг. на территории шести областей Республики Беларусь, с целью определения разнообразия эндемичных генетических вариантов главного аллергена пыльцы березы Bet v 1. Получены рекомбинантные векторные конструкции, содержащие гены, кодирующие различные изоформы изучаемого аллергена. Определена нуклеотидная последовательность клонированных фрагментов. Проведен анализ результатов исследования спектра изоформ белка Bet v 1. Полученные последовательности в той или иной степени соответствуют 11 генетическим вариантам изучаемого аллергена. В пределах одного дерева определено 7 изоформ Bet v 1. Преобладающей изоформой аллергена пыльцы березы Bet v 1 на территории Республики Беларусь является Bet v 1.0101 (Bet v 1a, X15877.1). Установленные варианты проанализированы на предмет их потенциальной аллергенности путем скрининга аминокислот, которые по данным литературы идентифицированы как влияющие на связывание IgE. Анализ аминокислотных остатков, входящих в состав IgE-связывающих конформационных эпитопов, выявил аминокислотные замены, проявляющие разнонаправленную (высокую или низкую) IgE-связывающую активность в положениях 31, 58, 113, 114, 126. Исследована структура доминантных эпитопов, распознаваемых рецептором Т-клеток. Обнаружено, что С-концевой иммунодоминантный Т-клеточный эпитоп Bet v 1143–157 является высококонсервативным среди различных изоформ аллергена, в отличие от эпитопа Bet v 178–93, расположенного в центральной области. Выявленные замены аминокислот изучаемых участков могут влиять на активацию Т-клеток, кросс-реактивность и существенно повышать вариативность ожидаемой IgE-опосредованной реакции.</p></abstract><trans-abstract xml:lang="en"><p>The hanging birch pollen collected in the period April – May 2020, 2021 in the territory of six regions of the Republic of Belarus was studied. Recombinant plasmid DNA was obtained. A nucleotide sequence of cloned fragments was determined. The results on the spectrum of isoforms of the Bet v 1 protein were analyzed. The obtained sequences corresponded to one degree or another to 11 genetic variants of the studied allergen. There were 7 isoforms of Bet v 1 defined within one tree. The predominant isoform of the birch pollen allergen Bet v 1 in the territory of the Republic of Belarus was Bet v 1.0101 (Bet v 1a, X15877.1). The identified variants were analyzed for their potential allergenicity by screening amino acids that according to the literature data were identified as affecting IgE-binding. The analysis of amino acid residues included in the IgE-binding conformational epitopes revealed amino acid substitutions exhibiting the multidirectional (high or low) IgE-binding activity in positions 31, 58, 113, 114, 126. The structure of dominant epitopes recognized by the T-cell receptor was studied. It was found that the C-terminal immunodominant T-cell epitope Bet v 1143–157 is highly conserved among various isoforms of the allergen in contrast to the epitope Bet v 178–93 located in the central region. The revealed amino acid substitutions of the studied sites can affect the activation of T-cells, cross-reactivity and significantly increase the variability of the expected IgE-mediated reaction.</p></trans-abstract><kwd-group xml:lang="ru"><kwd>Bet v 1</kwd><kwd>главный аллерген</kwd><kwd>пыльца березы</kwd><kwd>Betula pendula</kwd><kwd>PR-10</kwd><kwd>изоформы</kwd></kwd-group><kwd-group xml:lang="en"><kwd>Bet v 1</kwd><kwd>main allergen</kwd><kwd>birch pollen</kwd><kwd>Betula pendula</kwd><kwd>PR-10</kwd><kwd>isoforms</kwd></kwd-group></article-meta></front><back><ref-list><title>References</title><ref id="cit1"><label>1</label><citation-alternatives><mixed-citation xml:lang="ru">Breiteneder, H. The History and Science of the Major Birch Pollen Allergen Bet v 1 / H. Breiteneder, D. Kraft // Biomolecules. – 2023. – Vol. 13, N 7. – Art. 1151. https://doi.org/10.3390/biom13071151</mixed-citation><mixed-citation xml:lang="en">Breiteneder H., Kraft D. The History and Science of the Major Birch Pollen Allergen Bet v 1. Biomolecules, 2023, vol. 13, no. 7, art. 1151. https://doi.org/10.3390/biom13071151</mixed-citation></citation-alternatives></ref><ref id="cit2"><label>2</label><citation-alternatives><mixed-citation xml:lang="ru">Ligand recognition of the major birch pollen allergen Bet v 1 is isoform dependent / C. Seutter von Loetzen [et al.] // PLoS One. – 2015. – Vol. 10, N 6. – Art. e0128677. https://doi.org/10.1371/journal.pone.0128677</mixed-citation><mixed-citation xml:lang="en">von Loetzen C. S., Jacob T., Hartl-Spiegelhauer O., Vogel L., Schiller D., Spörlein-Güttler C., Schobert R., Vieths S., Hartl M. J., Rösch P. Ligand recognition of the major birch pollen allergen Bet v 1 is isoform dependent. PLoS One, 2015, vol. 10, no. 6, art. e0128677. https://doi.org/10.1371/journal.pone.0128677</mixed-citation></citation-alternatives></ref><ref id="cit3"><label>3</label><citation-alternatives><mixed-citation xml:lang="ru">Seven different genes encode a diverse mixture of isoforms of Bet v 1, the major birch pollen allergen / М. Schenk [et al.] // BMC Genomics. – 2006. – Vol. 7. – Art. 168. https://doi.org/10.1186/1471-2164-7-168</mixed-citation><mixed-citation xml:lang="en">Schenk M. F., Gilissen L. J., Esselink G. D., Smulders M. J. Seven different genes encode a diverse mixture of isoforms of Bet v 1, the major birch pollen allergen. BMC Genomics, 2006, vol. 7, art. 168. https://doi.org/10.1186/1471-2164-7-168</mixed-citation></citation-alternatives></ref><ref id="cit4"><label>4</label><citation-alternatives><mixed-citation xml:lang="ru">Naturally occurring hypoallergenic Bet v 1 isoforms fail to induce IgE responses in individuals with birch pollen allergy / S. Wagner [et al.] // J. Allergy Clin. Immunol. – 2008. – Vol. 121, N 1. – P. 246–252. https://doi.org/10.1016/j.jaci.2007.08.006</mixed-citation><mixed-citation xml:lang="en">Wagner S., Radauer C., Bublin M., Hoffmann-Sommergruber K., Kopp T., Greisenegger E. K., Vogel L., Vieths S., Scheiner O., Breiteneder H. Naturally occurring hypoallergenic Bet v 1 isoforms fail to induce IgE responses in individuals with birch pollen allergy. Journal of Allergy and Clinical Immunology, 2008, vol. 121, no. 1, pp. 246–252. https://doi.org/10.1016/j.jaci.2007.08.006</mixed-citation></citation-alternatives></ref><ref id="cit5"><label>5</label><citation-alternatives><mixed-citation xml:lang="ru">Purification and characterization of recombinant Bet v I, the major birch pollen allergen. Immunological equivalence to natural Bet v I / F. D. Ferreira [et al.] // J. Biol. Chem. – 1993. – Vol. 268, N 26. – P. 19574–19580. https://doi.org/10.1016/s0021-9258(19)36554-8</mixed-citation><mixed-citation xml:lang="en">Ferreira F. D., Hoffmann-Sommergruber K., Breiteneder H., Pettenburger K., Ebner C., Sommergruber W., Steiner R., Bohle B., Sperr W. R., Valent P. Purification and characterization of recombinant Bet v I, the major birch pollen allergen. Immunological equivalence to natural Bet v I. Journal of Biological Chemistry, 1993, vol. 268, no. 26, pp. 19574–19580. https://doi.org/10.1016/s0021-9258(19)36554-8</mixed-citation></citation-alternatives></ref><ref id="cit6"><label>6</label><citation-alternatives><mixed-citation xml:lang="ru">Proteomic profiling of birch (Betula verrucosa) pollen extracts from different origins / A. Erler [et al.] // Proteomics. – 2011. – Vol. 11, N 8. – P. 1486–1498. https://doi.org/10.1002/pmic.201000624</mixed-citation><mixed-citation xml:lang="en">Erler A., Hawranek T., Krückemeier L., Asam C., Egger M., Ferreira F., Briza P. Proteomic profiling of birch (Betula verrucosa) pollen extracts from different origins. Proteomics, 2011, vol. 11, no. 8, pp. 1486–1498. https://doi.org/10.1002/pmic.201000624</mixed-citation></citation-alternatives></ref><ref id="cit7"><label>7</label><citation-alternatives><mixed-citation xml:lang="ru">Isoforms of Bet v 1, the major birch pollen allergen, analyzed by liquid chromatography, mass spectrometry, and cDNA cloning / I. Swoboda [et al.] // J. Biol. Chem. – 1995. – Vol. 270, N 6. – P. 2607–2613. https://doi.org/10.1074/jbc.270.6.2607</mixed-citation><mixed-citation xml:lang="en">Swoboda I., Jilek A., Ferreira F., Engel E., Hoffmann-Sommergruber K., Scheiner O., Kraft D., Breiteneder H., Pittenauer E., Schmid E., Vicente O., Heberle-Bors E., Ahorn H., Breitenbach M. Isoforms of Bet v 1, the major birch pollen allergen, analyzed by liquid chromatography, mass spectrometry, and cDNA cloning. Journal of Biological Chemistry, 1995, vol. 270, no. 6, pp. 2607–2613. https://doi.org/10.1074/jbc.270.6.2607</mixed-citation></citation-alternatives></ref><ref id="cit8"><label>8</label><citation-alternatives><mixed-citation xml:lang="ru">Characterization of PR-10 genes from eight Betula species and detection of Bet v 1 isoforms in birch pollen / М. Schenk [et al.] // BMC Plant. Biol. – 2009. – Vol. 9. – Art. 24. https://doi.org/10.1186/1471-2229-9-24</mixed-citation><mixed-citation xml:lang="en">Schenk M. F., Cordewener J. H., America A. H., van’t Westende W. P., Smulders M. J., Gilissen L. J. Characterization of PR-10 genes from eight Betula species and detection of Bet v 1 isoforms in birch pollen. BMC Plant Biology, 2009, vol. 9, art. 24. https://doi.org/10.1186/1471-2229-9-24</mixed-citation></citation-alternatives></ref><ref id="cit9"><label>9</label><citation-alternatives><mixed-citation xml:lang="ru">Update of the WHO/IUIS Allergen Nomenclature Database based on analysis of allergen sequences / C. Radauer [et al.] // Allergy. – 2014. – Vol. 69, N 4. – P. 413–419. https://doi.org/10.1111/all.12348</mixed-citation><mixed-citation xml:lang="en">Radauer C., Nandy A., Ferreira F., Goodman R. E., Larsen J. N., Lidholm J., Pomés A., Raulf-Heimsoth M., Rozynek P., Thomas W. R., Breiteneder H. Update of the WHO/IUIS Allergen Nomenclature Database based on analysis of allergen sequences. Allergy, 2014, vol. 69, no. 4, pp. 413–419. https://doi.org/10.1111/all.12348</mixed-citation></citation-alternatives></ref><ref id="cit10"><label>10</label><citation-alternatives><mixed-citation xml:lang="ru">Allergen Nomenclature [Electronic resource] – Mode of access: http://www.allergen.org/index.php. – Date of access: 01.04.2024.</mixed-citation><mixed-citation xml:lang="en">Allergen Nomenclature. Available at: http://www.allergen.org/index.php (accessed 1 April 2024). 11. Bijli K. M., Singh B. P., Sridhara S., Arora N. Isolation of total RNA from pollens. Preparative Biochemistry and Biotechnology, 2001, vol. 31, no. 2, pp. 155–162. https://doi.org/10.1081/PB-100103381</mixed-citation></citation-alternatives></ref><ref id="cit11"><label>11</label><citation-alternatives><mixed-citation xml:lang="ru">Isolation of total RNA from pollens / K. Bijli [et al.] // Preparat. Biochem. Biotechnol. – 2001. – Vol. 31, N 2. – P. 155– 162. https://doi.org/10.1081/PB-100103381</mixed-citation><mixed-citation xml:lang="en">Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proceedings of the National Academy of Sciences of the United States of America, 1977, vol. 74, no. 12, pp. 5463–5467. https://doi.org/10.1073/pnas.74.12.5463</mixed-citation></citation-alternatives></ref><ref id="cit12"><label>12</label><citation-alternatives><mixed-citation xml:lang="ru">Sanger, F. DNA sequencing with chain-terminating inhibitors / F. Sanger, S. Nicklen, A. R. Coulson // Proc. Natl. Acad. Sci. U. S. A. – 1977. – Vol. 74, N 12. – P. 5463–5467. https://doi.org/10.1073/pnas.74.12.5463</mixed-citation><mixed-citation xml:lang="en">Basic Local Alignment Search. Available at: https://blast.ncbi.nlm.nih.gov/Blast.cgi. (accessed 1 April 2024)</mixed-citation></citation-alternatives></ref><ref id="cit13"><label>13</label><citation-alternatives><mixed-citation xml:lang="ru">Basic Local Alignment Search Tool [Electronic resource] – Mode of access: https://blast.ncbi.nlm.nih.gov/Blast.cgi. – Date of access: 01.04.2024.</mixed-citation><mixed-citation xml:lang="en">Hoffmann-Sommergruber K., Vanek-Krebitz M., Radauer C., Wen J., Ferreira F., Scheiner O., Breiteneder H. Genomic characterization of members of the Bet v 1 family: genes coding for allergens and pathogenesis-related proteins share intron positions. Gene, 1997, vol. 197, no. 1–2, pp. 91–100. https://doi.org/10.1016/S0378-1119(97)00246-1</mixed-citation></citation-alternatives></ref><ref id="cit14"><label>14</label><citation-alternatives><mixed-citation xml:lang="ru">Genomic characterization of members of the Bet v 1 family: genes coding for allergens and pathogenesis-related proteins share intron positions / K. Hoffmann-Sommergruber [et al.] // Gene. – 1997. – Vol. 197, N 1–2. – P. 91–100. https://doi.org/10.1016/S0378-1119(97)00246-1</mixed-citation><mixed-citation xml:lang="en">Gajhede M., Osmark P., Poulsen F. M., Ipsen H., Larsen J. N., Joost van Neerven R. J., Schou C., Løwenstein H., Spangfort M. D. X-ray and NMR structure of Bet v 1, the origin of birch pollen allergy. Nature Structural and Molecular Biology, 1996, vol. 3, pp. 1040–1045. https://doi.org/10.1038/nsb1296-1040</mixed-citation></citation-alternatives></ref><ref id="cit15"><label>15</label><citation-alternatives><mixed-citation xml:lang="ru">X-ray and NMR structure of Bet v 1, the origin of birch pollen allergy / M. Gajhede [et al.] // Nat. Struct. Mol. Biol. – 1996. – Vol. 3, N 12. – P. 1040–1045. https://doi.org/10.1038/nsb1296-1040</mixed-citation><mixed-citation xml:lang="en">Lund G., Christensen L. H., Ihlemann J., Andersen P. S., Wambre E., Würtzen P. A., Gupta S. T cells specific to multiple Bet v 1 peptides are highly cross-reactive toward the corresponding peptides from the homologous group of tree pollens. Frontiers in Immunology, 2023, vol. 14. https://doi.org/10.3389/fimmu.2023.1291666</mixed-citation></citation-alternatives></ref><ref id="cit16"><label>16</label><citation-alternatives><mixed-citation xml:lang="ru">T cells specific to multiple Bet v 1 peptides are highly cross-reactive toward the corresponding peptides from the homologous group of tree pollens / G. Lund [et al.] // Front. Immunol. – 2023. – Vol. 14. https://doi.org/10.3389/fimmu.2023.1291666</mixed-citation><mixed-citation xml:lang="en">Friedl-Hajek R., Radauer C., O’Riordain G., Hoffmann-Sommergruber K., Leberl K., Scheiner O., Breiteneder H. New Bet v 1 isoforms including a naturally occurring truncated form of the protein derived from Austrian birch pollen. Molecular Immunology, 1999, vol. 36, no. 10, pp. 639–645. https://doi.org/10.1016/s0161-5890(99)00078-4</mixed-citation></citation-alternatives></ref><ref id="cit17"><label>17</label><citation-alternatives><mixed-citation xml:lang="ru">New Bet v 1 isoforms including a naturally occurring truncated form of the protein derived from Austrian birch pollen / R. Friedl-Hajek [et al.] // Mol. Immunol. – 1999. – Vol. 36, N 10. – P. 639–645. https://doi.org/10.1016/s0161-5890(99)00078-4</mixed-citation><mixed-citation xml:lang="en">New Bet v 1 isoforms including a naturally occurring truncated form of the protein derived from Austrian birch pollen / R. Friedl-Hajek [et al.] // Mol. Immunol. – 1999. – Vol. 36, N 10. – P. 639–645. https://doi.org/10.1016/s0161-5890(99)00078-4</mixed-citation></citation-alternatives></ref></ref-list><fn-group><fn fn-type="conflict"><p>The authors declare that there are no conflicts of interest present.</p></fn></fn-group></back></article>
