Novel influenza viruses often cause differential infection patterns across different age groups, defined as heterogeneous demographic susceptibility. This occurred during the A/H2N2 pandemic, when children experienced higher influenza attack rates than adults. As the recognition of conserved epitopes across influenza subtypes by CD8+ cytotoxic T lymphocytes (CTLs) limit influenza disease, we hypothesised that conservation of CTL antigenic peptides (Ag-p) in viruses circulating before the pH2N2-1957 may have resulted in differential CTL immunity. We compared viruses isolated in the years preceding the pandemic (1941-1957) to which children and adults were exposed, with viruses circulating decades earlier (1918-1940), which could infect adults only. Consistent with phylogenetic models, influenza viruses circulating 1941-1957, which infected children, shared with pH2N2 the majority (~89%) of CTL-peptides within the most immunogenic nucleoprotein, matrix-1 and polymerase basic-1, thus providing evidence for minimal pH2N2 CTL escape in children. Our study, however, identified potential CTL immune evasion from pH2N2 irrespective of age, within HLA-A*03:01+ individuals for PB1471-L473V/N476I variants and HLA-B*15:01+ population for NP404-414-V408I mutant. Further experiments using the murine model of B-cell-deficient mice showed that multiple influenza infections resulted in superior protection from influenza-induced morbidity, coinciding with accumulation of tissue resident memory CD8+ T-cells in the lung. Our study suggests that protection against H2N2-1957 pandemic influenza was most likely linked to the number of influenza virus infections prior to the pandemic challenge rather than differential pre-existing CTL immunity. Thus, the regimen of a CTL-based vaccine/vaccine-component may benefit from periodic boosting to achieve fully protective, asymptomatic influenza infection.