Human leukocyte antigen (HLA) class I restricted epitope discovery in yellow fewer and dengue viruses: importance of HLA binding strength

dc.creatorLund, Ole
dc.creatorNascimento, Eduardo J. M.
dc.creatorMaciel, Milton
dc.creatorNielsen, Morten
dc.creatorLarsen, Mette Voldby
dc.creatorLundegaard, Claus
dc.creatorHarndahl, Mikkel
dc.creatorLamberth, Kasper
dc.creatorBuus, Søren
dc.creatorSalmon, Jérôme
dc.creatorAugust, Thomas J.
dc.creatorMarques, Ernesto T. A.
dc.date2018-09-11T12:09:38Z
dc.date2018-09-11T12:09:38Z
dc.date2011
dc.date.accessioned2023-09-26T20:56:36Z
dc.date.available2023-09-26T20:56:36Z
dc.identifierLUND, O. et al. Human leukocyte antigen (HLA) class I restricted epitope discovery in yellow fewer and dengue viruses: importance of HLA binding strength. PloS One, v. 6, n. 10, p. e26494, 2011.
dc.identifier1932-6203
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/28623
dc.identifier10.1371/journal.pone.0026494
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8866564
dc.descriptionEste trabalho foi apoiado por contratos NIAID HHSN266200400083C, HHSN266200400025C ( http://www.niaid.nih.gov/ ).
dc.descriptionEpitopes from all available full-length sequences of yellow fever virus (YFV) and dengue fever virus (DENV) restricted by Human Leukocyte Antigen class I (HLA-I) alleles covering 12 HLA-I supertypes were predicted using the NetCTL algorithm. A subset of 179 predicted YFV and 158 predicted DENV epitopes were selected using the EpiSelect algorithm to allow for optimal coverage of viral strains. The selected predicted epitopes were synthesized and approximately 75% were found to bind the predicted restricting HLA molecule with an affinity, K(D), stronger than 500 nM. The immunogenicity of 25 HLA-A*02:01, 28 HLA-A*24:02 and 28 HLA-B*07:02 binding peptides was tested in three HLA-transgenic mice models and led to the identification of 17 HLA-A*02:01, 4 HLA-A*2402 and 4 HLA-B*07:02 immunogenic peptides. The immunogenic peptides bound HLA significantly stronger than the non-immunogenic peptides. All except one of the immunogenic peptides had K(D) below 100 nM and the peptides with K(D) below 5 nM were more likely to be immunogenic. In addition, all the immunogenic peptides that were identified as having a high functional avidity had K(D) below 20 nM. A*02:01 transgenic mice were also inoculated twice with the 17DD YFV vaccine strain. Three of the YFV A*02:01 restricted peptides activated T-cells from the infected mice in vitro. All three peptides that elicited responses had an HLA binding affinity of 2 nM or less. The results indicate the importance of the strength of HLA binding in shaping the immune response.
dc.formatapplication/pdf
dc.languageeng
dc.publisherMan-Seong Park, Faculdade de Medicina da Universidade de Hallym, República da Coréia
dc.rightsopen access
dc.subjectAntígenos
dc.subjectResposta imune
dc.subjectImunoensaios ligados a enzimas
dc.subjectCélulas T
dc.subjectVacinas
dc.subjectAntigens
dc.subjectImmune response
dc.subjectEnzyme-linked immunoassays
dc.subjectT cells
dc.subjectVaccines
dc.subjectVírus da Dengue / imunologia
dc.subjectEpitopos / imunologia
dc.subjectAntígenos de Histocompatibilidade Classe I / imunologia
dc.subjectHumanos
dc.subjectRatos transgênicos
dc.subjectDados de Sequencia Molecular
dc.subjectVacina contra Febre Amarela / imunologia
dc.subjectVírus da febre amarela / imunologia
dc.titleHuman leukocyte antigen (HLA) class I restricted epitope discovery in yellow fewer and dengue viruses: importance of HLA binding strength
dc.typeArticle


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