Immunogenicity of HLA Class I and II Double Restricted Influenza A-Derived Peptides.

The aim of the present study was to identify influenza A-derived peptides which bind to both HLA class I and -II molecules and by immunization lead to both HLA class I and class II restricted immune responses. Eight influenza A-derived 9-11mer peptides with simultaneous binding to both HLA-A*02:01 a...

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Main Authors: Sara Ram Pedersen, Jan Pravsgaard Christensen, Søren Buus, Michael Rasmussen, Karen Smith Korsholm, Morten Nielsen, Mogens Helweg Claesson
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2016-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4701504?pdf=render
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author Sara Ram Pedersen
Jan Pravsgaard Christensen
Søren Buus
Michael Rasmussen
Karen Smith Korsholm
Morten Nielsen
Mogens Helweg Claesson
author_facet Sara Ram Pedersen
Jan Pravsgaard Christensen
Søren Buus
Michael Rasmussen
Karen Smith Korsholm
Morten Nielsen
Mogens Helweg Claesson
author_sort Sara Ram Pedersen
collection DOAJ
description The aim of the present study was to identify influenza A-derived peptides which bind to both HLA class I and -II molecules and by immunization lead to both HLA class I and class II restricted immune responses. Eight influenza A-derived 9-11mer peptides with simultaneous binding to both HLA-A*02:01 and HLA-DRB1*01:01 molecules were identified by bioinformatics and biochemical technology. Immunization of transgenic HLA-A*02:01/HLA-DRB1*01:01 mice with four of these double binding peptides gave rise to both HLA class I and class II restricted responses by CD8 and CD4 T cells, respectively, whereas four of the double binding peptides did result in HLA-A*02:01 restricted responses only. According to their cytokine profile, the CD4 T cell responses were of the Th2 type. In influenza infected mice, we were unable to detect natural processing in vivo of the double restricted peptides and in line with this, peptide vaccination did not decrease virus titres in the lungs of intranasally influenza challenged mice. Our data show that HLA class I and class II double binding peptides can be identified by bioinformatics and biochemical technology. By immunization, double binding peptides can give rise to both HLA class I and class I restricted responses, a quality which might be of potential interest for peptide-based vaccine development.
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spelling doaj.art-a3f575c9eb6b4fbdb293449a66de05752022-12-21T23:19:43ZengPublic Library of Science (PLoS)PLoS ONE1932-62032016-01-01111e014562910.1371/journal.pone.0145629Immunogenicity of HLA Class I and II Double Restricted Influenza A-Derived Peptides.Sara Ram PedersenJan Pravsgaard ChristensenSøren BuusMichael RasmussenKaren Smith KorsholmMorten NielsenMogens Helweg ClaessonThe aim of the present study was to identify influenza A-derived peptides which bind to both HLA class I and -II molecules and by immunization lead to both HLA class I and class II restricted immune responses. Eight influenza A-derived 9-11mer peptides with simultaneous binding to both HLA-A*02:01 and HLA-DRB1*01:01 molecules were identified by bioinformatics and biochemical technology. Immunization of transgenic HLA-A*02:01/HLA-DRB1*01:01 mice with four of these double binding peptides gave rise to both HLA class I and class II restricted responses by CD8 and CD4 T cells, respectively, whereas four of the double binding peptides did result in HLA-A*02:01 restricted responses only. According to their cytokine profile, the CD4 T cell responses were of the Th2 type. In influenza infected mice, we were unable to detect natural processing in vivo of the double restricted peptides and in line with this, peptide vaccination did not decrease virus titres in the lungs of intranasally influenza challenged mice. Our data show that HLA class I and class II double binding peptides can be identified by bioinformatics and biochemical technology. By immunization, double binding peptides can give rise to both HLA class I and class I restricted responses, a quality which might be of potential interest for peptide-based vaccine development.http://europepmc.org/articles/PMC4701504?pdf=render
spellingShingle Sara Ram Pedersen
Jan Pravsgaard Christensen
Søren Buus
Michael Rasmussen
Karen Smith Korsholm
Morten Nielsen
Mogens Helweg Claesson
Immunogenicity of HLA Class I and II Double Restricted Influenza A-Derived Peptides.
PLoS ONE
title Immunogenicity of HLA Class I and II Double Restricted Influenza A-Derived Peptides.
title_full Immunogenicity of HLA Class I and II Double Restricted Influenza A-Derived Peptides.
title_fullStr Immunogenicity of HLA Class I and II Double Restricted Influenza A-Derived Peptides.
title_full_unstemmed Immunogenicity of HLA Class I and II Double Restricted Influenza A-Derived Peptides.
title_short Immunogenicity of HLA Class I and II Double Restricted Influenza A-Derived Peptides.
title_sort immunogenicity of hla class i and ii double restricted influenza a derived peptides
url http://europepmc.org/articles/PMC4701504?pdf=render
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