Resident memory T cells (TRM) in the lung are vital for heterologous protection against influenza A virus (IAV). Environmental factors are necessary to establish lung TRM; 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 TRM 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 TRM formation in the lung elicited by lower affinity TCR stimulation. TCR affinity did not impact the overall phenotype or long-term maintenance of lung TRM. Overall, these findings demonstrate that TRM formation is negatively correlated with increased TCR signal strength. Lower affinity cells may have an advantage in forming TRM to ensure diversity in the Ag-specific repertoire in tissues.
Bibliographical noteFunding Information:
This work was supported by National Institutes of Health (NIH) Grant K22 AI110581 and NIH Grant R01 AI132962 (to R.A.L.). J.K.F. was supported by NIH Grant T32 HL007741 and E.J.F. by NIH Grant T32 AI007313. This project was also funded in part with federal funds from the National Institute of Allergy and Infectious Diseases, the NIH, and the Department of Health and Human Services under Centers of Excellence for Influenza Research and Surveillance Contract HHSN272201400005C.