Clonally expanded tissue resident CD8+ T cells recognize conserved influenza viral proteins in the lower airways during acute human influenza infection 2336

Abstract Description Seasonal influenza viruses are a common cause of human morbidity and mortality. Airway tissue-resident CD8+ T cells are perfectly positioned to protect against influenza viruses. However, the molecular signatures and antigen specificity of such T cells during acute human infection are unstudied. We analyzed circulating and airway CD8+ T cells from four age-matched naturally influenza B virus (IBV)-infected subjects. We sequenced 35,854 T cells, 24,858 from blood, and 10,996 from bronchoalveolar lavage (BAL) cellular material. We observed oligoclonal T cell receptor (TCR) expansion in all four subjects, where the most frequent clonal TCR in each subject composed between 8% and 62% of T cells in the BAL. We reverse epitope mapped each subject’s highest frequency paired TCRs. The highest frequency TCRs were IBV specific, and 16 of 20 recognized phylogenetically conserved internal IBV proteins. Transcriptional analysis revealed that airway IBV-specific CD8+ T cells showed clear tissue-resident memory signatures. IBV-specific CD8+ T cells in the airway were in a state of heightened immune surveillance and displayed high interferon-gamma expression. Our results show that clonally expanded influenza-specific CD8+ T cells recognizing only a handful of conserved epitopes mediate the tissue-resident response in the lower airways of humans during acute seasonal influenza infection. Funding Sources NIH R01AI173203 Topic Categories Mucosal and Regional Immunology (MUC)