The influenza virus is responsible for yearly epidemics that account for approximately 650,000 deaths worldwide, despite vaccines being widely available. Novel vaccine technologies targeting CD8+ T cells are attractive as they are known to recognise conserved peptides of influenza viruses. This is significant as we can target several influenza strains in single a vaccine.
Activating CD8+ T cells require peptides to be presented by the highly polymorphic Human Leukocyte Antigen class I (HLA-I) molecules. These different HLA-I molecules have different peptide-binding preferences, making peptide selection for inclusion in a vaccine difficult. However, several HLA-I molecules have similar peptide presenting preferences and these are
grouped into superfamilies.
Targeting peptides presented by several HLA-I molecules in future vaccines may enhance our capacity to induce protection across several broad and diverse populations. We investigated this phenomenon in the HLA-B44 superfamily using the NS1195-203, which is known to induce CD8+ T cell responses in HLA-B*44:03 individuals.
Using in silico computer predictions, we first visualised how the different HLA-I molecules were presenting the peptide. We identified that HLA-B*44:02 and HLA-B*44:03 were most likely to present NS1195-203 to T cells.
We then used T cell activation assays to assess whether the NS1195-203 peptide induces CD8+ T cell responses in individuals with the different HLA-I molecules. We found that only HLA-B*44:03+ and HLA-B*44:02+ individuals had any measurable CD8+ T cell response, in line with our structural predictions.
These data suggests that although peptides can be presented by multiple HLAs in the same HLA-I superfamily, it may not induce any, or the same level of response. This therefore warrants further investigation into other peptides to assess whether we should target HLA superfamilies or future therapeutics.