Overarching Immunodominance Patterns and Substantial Diversity in Specificity and Functionality in the Circulating Human Influenza A and B CD4 T Cell Repertoire

There is limited information on the antigen specificity and functional potential of the influenza-specific CD4 T cell repertoire in humans. Here, ELISPOT assays were used to examine circulating CD4 T cell influenza specificities directly ex vivo in healthy adults. Our studies revealed CD4 T cell reactivity to multiple influenza proteins, including hemagglutinins, NA, M1 and NP. Unexpectedly, the immunodominance hierarchies and functional potential of cells reactive toward influenza A were distinct from influenza B. We also identified influenza-specific cells producing granzyme B. Our findings revealed individual and virus-specific patterns that may differentially poise humans to respond to infection or vaccination.