The Impact of TCR Signal Strength on Resident Memory T Cell Formation during Influenza Virus Infection

Resident memory T cells (T-RM) in the lung are vital for heterologous protection against influenza A virus (IAY). Environmental factors are necessary to establish lung T-RM; however, the role of T cell-intrinsic factors like TCR signal strength have not been elucidated. In this study, we investigated the impact of TCR signal strength on the generation and maintenance of lung T-RM after IAV infection. We inserted high- and low-affinity OT-I epitopes into IAV and infected mice after transfer of OT-I T cells. We uncovered a bias in T-RM formation in the lung elicited by lower affinity TCR stimulation. TCR affinity did not impact the overall phenotype or long-term maintenance of lung T-RM. Overall, these findings demonstrate that T-RM formation is negatively correlated with increased TCR signal strength. Lower affinity cells may have an advantage in forming T-RM to ensure diversity in the Ag-specific repertoire in tissues.