Influenza-specific T-cell receptor (TCR)
- Influenza specific TCR
- Highly conserved epitope
- Several possible applications including new therapeutics, cellular therapy and vaccination
Influenza viruses cause severe and life threatening diseases in humans. Besides the known human influenza viruses, several other influenza virus species from animals such as swine or avian influenza exist, that are capable to be transferred to humans. Since influenza viruses are highly mutable, there is an ongoing threat of severe epidemics by mutated influenza viruses.
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The invention is based on the identification and isolation of the TCR genes of influenza-specific cytotoxic T-lymphocytes (CTL) that can be used for therapy and prevention of influenza infections. The TCR recognizes a viral epitope (GILGFVFTL) in the influenza matrix, which is highly conserved in all influenza virus variants including human, swine and avian influenza. The epitope is presented by the HLA-A2, the most frequent HLA serotype worldwide (about 40% in Central Europe). The TCRs could be used for treatment of infected patients and for the preventive genetic immunization of healthy persons in the case of an emerging epidemic with a new virulent influenza strain.
- as soluble TCR, fused to e.g. Fc receptor/Fc domain/cytokines/toxins/antibodies
- in cellular therapy, both autologous and allogenic; interesting for patients with life threatening drug resistant influenza infection, or new influenza variants when no vaccine is available yet
- in vaccine research, e.g. TCR transfected cells as standardized tool to check immunogenicity of attenuated vaccines (esp. in case of escape mutants)
- for genetic vaccination, esp. against highly pathogenic viruses such as avian flu without effective vaccine