Identification of immunodominant CD8 epitope in the stalk domain of influenza B viral hemagglutinin
- Centre for Biologics Evaluation, Biologics and Genetic Therapies Directorate, HPFB, Health Canada and WHO Collaborating Center for Standardization and Evaluation of Biologicals, 251 Sir Frederick Banting Driveway, K1A 0K9, Ottawa, ON (Canada)
- National Institute for Food and Drug Control and WHO Collaborating Center for Standardization and Evaluation of Biologicals, No.2, Tiantan Xili, Beijing (China)
- National Microbiology Laboratory, Public Health Agency of Canada, 1015 Arlington St, Winnipeg, MB (Canada)
- Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, University of Ottawa, Roger Guindon Campus, Ottawa, ON (Canada)
Highlights: • The HA2 subunit of influenza hemagglutinin is highly conserved and could be a potential candidate for a universal vaccine. • CD8 T cells are important for influenza viral clearance from the lungs. • Assessment of CD8 T cell-induced immunity is critical for vaccine evaluation. • Immunodominant H-2K{sup d}-restricted peptide, YYSTAASSL, was found to effectively induce cell-mediated immune responses. • YYSTAASSL induces high levels of IL-2, TNF-α and cytotoxic CD8 T cells. Human infections by type B influenza virus constitute about 25% of all influenza cases. The viral hemagglutinin is comprised of two subunits, HA1 and HA2. While HA1 is constantly evolving in an unpredictable fashion, the HA2 subunit is highly conserved, making it a potential candidate for a universal vaccine. However, immunodominant epitopes in the HA2 subunit remain largely unknown. To delineate MHC Class I epitopes, we first identified 9-mer H-2K{sup d}-restricted CD8 T cell epitopes in the HA2 domain by in silico analyses, followed by evaluating the immunodominance of these peptides in mice challenged with the virus. Of three peptides selected through in silico analysis, the universally conserved peptide, YYSTAASSL (B/HA2-190), possessed the highest predicted binding affinity to MHC Class I and was most effective in inducing IL-2 and TNF-α in mouse splenocytes. Importantly, the peptide demonstrated best capability of stimulating peptide-specific ex-vivo cytotoxicity against target cells. Taken together, this finding would be of value for assessment of cell-mediated immune responses elicited by vaccines based on the highly conserved HA2 stalk domain.
- OSTI ID:
- 23136981
- Journal Information:
- Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 502; ISSN 0006-291X; ISSN BBRCA9
- Country of Publication:
- United States
- Language:
- English
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