Monitoring of human antiviral immunity using MHC class I tetramers in influenza

Evaluation of specific immune response in either influenza infected or immunized humans have been considered as the only reliable indicator of protective immunity and virus resistance. Antiviral immunity has usually been assessed by antiviral antibody determination in paired sera (serocoversion). This method evaluates only the capacity of B cells to secrete antiviral antibodies while T cells, as the most important cells in antiviral immune reactions are not directly analysed. We used new MHC tetramer technology with an attempt to quantify ex vivo influenza specific T cells. Enumeration of CD8+ influenza specific T cells requires cognate recognition of the complex T cell receptor/antigen by Class I MHC. This was achieved using custom designated HLA-A*0201-restricted influenza matrix protein (FLU) tetramer. Influenza infection was confirmed with direct fluorescent assay (DFA) in nasopharyngeal swabs and with inhibition of hemagglutination (IH) assay in sera. We showed that during acute phase of infection, HLA-A*0201 positive patients with confirmed influenza infection had influenza-specific T cells, while these cells were not present in peripheral blood of HLA-A*0201 positive patients without influenza infection. These results indicate that MHC tetramer method can be used to distinguish influenza infection from other infections that cause similar symptoms in patients.