Immunogenicity of HLA Class I and II Double Restricted Influenza A-Derived Peptides
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Immunogenicity of HLA Class I and II Double Restricted Influenza A-Derived Peptides. / Pedersen, Sara Ram; Christensen, Jan Pravsgaard; Buus, Søren; Rasmussen, Michael; Korsholm, Karen Smith; Nielsen, Morten; Claesson, Mogens Helweg.
In: P L o S One, Vol. 11, No. 1, e0145629, 2016.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Immunogenicity of HLA Class I and II Double Restricted Influenza A-Derived Peptides
AU - Pedersen, Sara Ram
AU - Christensen, Jan Pravsgaard
AU - Buus, Søren
AU - Rasmussen, Michael
AU - Korsholm, Karen Smith
AU - Nielsen, Morten
AU - Claesson, Mogens Helweg
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
U2 - 10.1371/journal.pone.0145629
DO - 10.1371/journal.pone.0145629
M3 - Journal article
C2 - 26731261
VL - 11
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 1
M1 - e0145629
ER -
ID: 163776931