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Human memory CTL response specific for influenza A virus is broad and multispecific
C Gianfrani1, C Oseroff, J Sidney
1Department of Immunology, Epimmune Inc., San Diego, CA 92121, USA.
Human Immunology
|April 25, 2000
Summary
This study reveals a broader range of influenza A virus-specific memory cytotoxic T-lymphocyte (CTL) responses in humans than previously thought. These findings have implications for developing more effective multiepitope vaccines against influenza.
Area of Science:
- Immunology
- Virology
- Vaccinology
Background:
- Class I restricted cytotoxic T-lymphocyte (CTL) responses are typically focused on a few immunodominant epitopes.
- Influenza A (FLU) virus matrix 58-66 specific memory CTL activity in HLA-A2 individuals is a known example of narrow focus.
Purpose of the Study:
- To analyze the repertoire of memory, FLU-specific CTLs in individuals with HLA-A2 and HLA-A11.
- To identify novel FLU-specific CTL epitopes beyond the dominant ones.
Main Methods:
- Screening of HLA-A2 and HLA-A11 binding peptides from the FLU-Puerto Rico/8/34 (PR8) isolate.
- Testing peptide immunogenicity in HLA-A2.1/Kb and HLA-A11/Kb transgenic mice.
- Assessing recall CTL responses from human peripheral blood mononuclear cells (PBMCs) and lymphocytes.
Main Results:
- Identification of 5 new FLU-specific CTL epitopes in HLA-A2 individuals, in addition to the known M1.58.
- Identification of 8 FLU-specific CTL epitopes in HLA-A11 individuals.
- Discovery that several identified epitopes are conserved across FLU isolates and bind multiple HLA supertypes.
- Identification of 37 HLA-B7 binding peptides.
Conclusions:
- A previously unappreciated breadth of FLU-specific memory CTL responses exists in humans.
- These findings support the development of multiepitope vaccines targeting a wider range of influenza epitopes.