Human CD8+ T cell cross-reactivity across influenza A, B and C viruses

Abstract

Influenza A, B and C viruses (IAV, IBV, ICV) circulate globally and infect humans, with IAV/IBV causing most severe disease. While CD8 + T-cells confer cross-protection against different IAV strains, CD8 + T-cell responses to IBV/ICV are understudied. We dissected the CD8 + T-cell cross-reactome against influenza viruses and provided the first evidence of CD8 + T-cell cross-reactivity across IAV, IBV and ICV. Using immunopeptidomics, we identified immunodominant CD8 + T-cell epitopes from IBV, protective in mice, and found prominent memory CD8 + T-cells towards both universal and influenza type-specific epitopes in blood and lungs of healthy humans, with lung-derived CD8 + T-cells displaying a tissue-resident phenotype. Importantly, effector CD38 + Ki67 + CD8 + T-cells against novel epitopes were readily detected in IAV-and IBV-infected pediatric and adult patients. Our study introduces a new paradigm, whereby CD8 + T-cells confer unprecedented cross-reactivity across all influenza viruses, a key finding for designing universal vaccines.

Human γδ T‐cell receptor repertoire is shaped by influenza viruses, age and tissue compartmentalisation

“…Umbilical CB was obtained from Mercy Hospital for Women (Heidelberg, Australia). Influenza B virus infection was confirmed in three donors with nasal swabs which were PCR positive for IBV . In donor AH040, two timepoints were available, D7 and D30 post‐disease onset.…”

Epidemiology and Clinical Characteristics of Influenza C Virus

“…HEF is the major target for host neutralizing antibodies, which appear to bind to epitopes near the receptor-binding site and the esterase site [37][38][39][40][41][42]. Human CD8+ T cells recognize epitopes of ICV internal proteins, some of which are conserved in IAV and IBV [43]. M1, encoded from segment 6, is the major structural protein of ICV that lies under the lipid bilayer [44,45].…”

Life course exposures continually shape antibody profile and risk of seroconversion to influenza

“…3 D and H) could suggest low HAI antibody among this age group, which could be due to high non-specific immune responses [e.g. antibodies against HA stalk and neuraminidase (NA) and cellular immune responses; (18)(19)(20)(21)(22)]. These non-specific immunities, which may accumulate over multiple exposures and are not measured in our assay, could preventing people from being infected and producing updated, strain specific HA responses (19,20,23).…”

“…Another plausible hypothesis is that non-HAI immunity that was acquired from previous infections (e.g. antibody to HA stalk and NA and cellular immune responses) could blunt the production of strain-specific antibody upon exposure to circulating strains (18)(19)(20)(21), thus reducing the HAI titers to the circulating strains and increasing the probability of seroconversion. High antibody to non-recent strains could indicate individuals who have not experienced infection in recent times [e.g.…”