Abstract
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.
Highlights
HLA class I and II molecules are of importance for influenza virus processing and clearance
The overall agreement between the predicted and measured binding values is high. 15 peptides were measured to bind to HLA-AÃ02:01 with high affinity (KD < 100 nM), and only one peptide failed to bind HLA-AÃ02:01.Eight of the peptides were measured to bind to HLA-DRB1Ã01:01 with a KD value below 200 nM
We have previously identified CD8 and CD4 T cell reactivity towards HLA class I and class II double binding immunogenic 9mer influenza A-derived peptides in the peripheral blood of healthy adult blood donors
Summary
HLA class I and II molecules are of importance for influenza virus processing and clearance. Cytotoxic, influenza-specific CD8 T cells are important for terminating the acute infection and they contribute to long-term immunity [1,2]. We have previously identified 34 new HLA-class I binding influenza A-derived antigenic 9-mer peptides, which collectively bind to the twelve HLA class I supertypes [4,5], globally covering HLA by > 99%. Eighteen of these peptides gave rise exclusively to HLA.
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