{"title":"A STRATEGY FOR DIRECT DELIVERY OF ANTIGENIC CONSTRUCTS TO DENDRITIC CELL RECEPTORS","authors":"Anzhelika Melnikova, Tatiana Mushkarina, Lyudmila Grivtsova","doi":"10.1016/j.htct.2024.04.011","DOIUrl":null,"url":null,"abstract":"<div><h3>Objective</h3><p>C-type lectin receptors (CLRs) expressed by DC are considered attractive targets for effective targeting of antigen to antigen-presenting cells, since the participation of CLRs can additionally stimulate antigen presentation and, accordingly, subsequent activation of T cells. To study the ability of DC to enhance antigen capture and presentation using a library of fluorescein-labeled polyacrylamide glycoconjugates.</p></div><div><h3>Methodology</h3><p>DC was obtained by culturing human peripheral blood monocytes in a complete RPMI-1640 nutrient medium containing GM-CSF, IL-4 and TNFa. Immunophenotypes were analyzed using flow cytometric analysis. In our study, synthetic FSL (Function-Spacer-Lipid) constructs will be used: polyacrylamide glycoconjugate (Adi-sp)3-βDD-PAA-Fluo, conjugate N-acetyllactosamine, glycolipid (Adi-sp)3-βDD ((Adi-sp)3-βDD-DOPE). Next, the binding of these cells to glycoprobes was investigated.</p></div><div><h3>Results</h3><p>A new class of glycoconjugates specific for binding to C-type lectin receptors has been synthesized. The key cytokines for the cultivation of DC are GM-CSF (final concentration 80 ng/ml), IL-4 (final concentration 10 ng/ml), as well as differentiation inducers: TNF-α, PGE2. Mapping of human blood cells using a library of fluorescein-labeled polyacrylamide glycoconjugates showed that the studied glycoprobes bind to more than 15% of the human leukocyte population.</p></div><div><h3>Conclusion</h3><p>In our proposed research project, a new approach will be used to study the strategy of enhancing the capture and presentation of antigen by dendritic cells by targeting C-type lectin receptors.</p></div>","PeriodicalId":12958,"journal":{"name":"Hematology, Transfusion and Cell Therapy","volume":null,"pages":null},"PeriodicalIF":1.8000,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2531137924000932/pdfft?md5=3280085fb110ea4bd524202cfc5dff64&pid=1-s2.0-S2531137924000932-main.pdf","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Hematology, Transfusion and Cell Therapy","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2531137924000932","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"HEMATOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Objective
C-type lectin receptors (CLRs) expressed by DC are considered attractive targets for effective targeting of antigen to antigen-presenting cells, since the participation of CLRs can additionally stimulate antigen presentation and, accordingly, subsequent activation of T cells. To study the ability of DC to enhance antigen capture and presentation using a library of fluorescein-labeled polyacrylamide glycoconjugates.
Methodology
DC was obtained by culturing human peripheral blood monocytes in a complete RPMI-1640 nutrient medium containing GM-CSF, IL-4 and TNFa. Immunophenotypes were analyzed using flow cytometric analysis. In our study, synthetic FSL (Function-Spacer-Lipid) constructs will be used: polyacrylamide glycoconjugate (Adi-sp)3-βDD-PAA-Fluo, conjugate N-acetyllactosamine, glycolipid (Adi-sp)3-βDD ((Adi-sp)3-βDD-DOPE). Next, the binding of these cells to glycoprobes was investigated.
Results
A new class of glycoconjugates specific for binding to C-type lectin receptors has been synthesized. The key cytokines for the cultivation of DC are GM-CSF (final concentration 80 ng/ml), IL-4 (final concentration 10 ng/ml), as well as differentiation inducers: TNF-α, PGE2. Mapping of human blood cells using a library of fluorescein-labeled polyacrylamide glycoconjugates showed that the studied glycoprobes bind to more than 15% of the human leukocyte population.
Conclusion
In our proposed research project, a new approach will be used to study the strategy of enhancing the capture and presentation of antigen by dendritic cells by targeting C-type lectin receptors.