Generating protective immunity to severe influenza disease in Indigenous Australians

Autor: Luca Hensen, Patricia Illing, Louise Rowntree, Jennifer Habel, Nicole Mifsud, Marios Koutsakos, Liyen Loh, Carolien van de Sandt, Andrea Nguyen, Stephanie Gras, Steve Rockman, Adrian Miller, Oanh Nguyen, Bridie Clemens, Steven Tong, Anthony Purcell, Katherine Kedzierska
Rok vydání: 2020
Předmět:
Zdroj: The Journal of Immunology. 204:93.15-93.15
ISSN: 1550-6606
0022-1767
DOI: 10.4049/jimmunol.204.supp.93.15
Popis: The 2009 influenza pandemic caused generally mild infections due, at least partially, to broadly cross-reactive pre-existing CD8+ T cell immunity. In contrast, severe disease was observed in Indigenous populations worldwide, as shown by disproportionate hospitalisation rates. Human leukocyte antigen-I (HLA-I) molecules present viral peptides to CD8+ T cells, eliciting anti-viral responses that contribute to accelerated viral clearance. We identified several HLA-I alleles which are highly prevalent in Indigenous Australians (HLA-A*11:01, A*24:02, A*34:01, B*13:01 and B*15:21) but largely understudied. Using specific HLA-allomorph expressing C1R cell lines, we identified influenza A and B immunopeptidomes by mass spectrometry. A total of 653 influenza peptides derived from various viral proteins were presented during infection by different HLA-Is. Using virus-specific PBMC expansions, we screened these peptides for their potential to reactivate influenza-specific memory CD8+ T cells. We identified on average 4.6 (2–8) immunogenic epitopes per HLA-I for influenza A and B. We defined epitope-specific CD8+ T cells ex vivo across different human tissues and determined their memory subsets, phenotype and activation in healthy donors and influenza-infected patients. Overall, our approach is effective in detection of immunogenic epitopes and understanding CD8+ T cell pools in Indigenous populations, thus providing potential vaccine targets to protect Indigenous populations globally, from severe influenza disease. This is the first study to identify hallmarks of immunogenic responses and reveal key targets of an effective CD8+ T cell vaccine in Indigenous people.
Databáze: OpenAIRE
Externí odkaz: