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

Lund, O and Nascimento, EJM and Maciel, M and Nielsen, M and Larsen, M and Lundegaard, C and Harndahl, M and Lamberth, K and Buus, S and Salmon, J and August, TJ and Marques, ETA (2011) Human leukocyte antigen (HLA) class i restricted epitope discovery in yellow fewer and dengue viruses: Importance of HLA binding strength. PLoS ONE, 6 (10).

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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, 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. © 2011 Lund et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Lund, O
Nascimento, EJMejmn@pitt.eduEJMN
Maciel, M
Nielsen, M
Larsen, M
Lundegaard, C
Harndahl, M
Lamberth, K
Buus, S
Salmon, J
August, TJ
Marques, ETAmarques@pitt.eduMARQUES0000-0003-3826-9358
Contributors:
ContributionContributors NameEmailPitt UsernameORCID
EditorPark, Man-SeongUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Centers: Other Centers, Institutes, Offices, or Units > Center for Vaccine Research
Date: 25 October 2011
Date Type: Publication
Journal or Publication Title: PLoS ONE
Volume: 6
Number: 10
DOI or Unique Handle: 10.1371/journal.pone.0026494
Schools and Programs: Graduate School of Public Health > Infectious Diseases and Microbiology
Refereed: Yes
Related URLs:
MeSH Headings: Amino Acid Sequence; Animals; Dengue Virus--immunology; Enzyme-Linked Immunosorbent Assay; Epitopes--chemistry; Epitopes--immunology; Histocompatibility Antigens Class I--immunology; Humans; Mice; Mice, Transgenic; Molecular Sequence Data; Yellow Fever Vaccine--immunology; Yellow fever virus--immunology
Other ID: NLM PMC3198402
PubMed Central ID: PMC3198402
PubMed ID: 22039500
Date Deposited: 19 Sep 2012 22:18
Last Modified: 17 Jul 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/13986

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