NDLI: Human Leukocyte Antigen (HLA) Class I Restricted Epitope Discovery in Yellow Fewer and Dengue Viruses: Importance of HLA Binding Strength

Content Provider	PubMed Central
Author	Lund, Ole Nascimento, Eduardo J. M. Maciel, Milton Nielsen, Morten Larsen, Mette Voldby Lundegaard, Claus Harndahl, Mikkel Lamberth, Kasper Buus, Søren Salmon, Jérôme August, Thomas J. Marques, Ernesto T. A.
Editor	Park, Man-seong
Copyright Year	2011
Abstract	Epitopes 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, KD, stronger than 500 nM. The immunogenicity of 25 HLA-A02:01, 28 HLA-A24:02 and 28 HLA-B07:02 binding peptides was tested in three HLA-transgenic mice models and led to the identification of 17 HLA-A02:01, 4 HLA-A2402 and 4 HLA-B07:02 immunogenic peptides. The immunogenic peptides bound HLA significantly stronger than the non-immunogenic peptides. All except one of the immunogenic peptides had KD below 100 nM and the peptides with KD 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 KD below 20 nM. A02:01 transgenic mice were also inoculated twice with the 17DD YFV vaccine strain. Three of the YFV A02:01 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.
Related Links	http://dx.doi.org/10.1371/journal.pone.0026494
Starting Page	26494
File Format	PDF
ISSN	19326203
e-ISSN	19326203
Journal	PLoS ONE
Issue Number	10
Volume Number	6
Language	English
Publisher	Public Library of Science
Publisher Date	2011-10-01
Access Restriction	Open
Rights Holder	Public Library of Science
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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