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

Abstract

Resident memory T cells (T RM) in the lung are vital for heterologous protection against influenza A virus (IAV). 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.

Circulating memory CD8+ T cells are limited in forming CD103+ tissue‐resident memory T cells at mucosal sites after reinfection

“…Thus, T CM cells appear to be able to contribute to resident memory at mucosal sites under certain conditions. The capacity of T CM cells to form secondary T RM cells may be shaped by TCR affinity [57,58], which could explain differences in the offspring of monoclonal and polyclonal T CM populations. Moreover, competing cell populations, including activated T N cells and pre-existing T RM cells, may affect the formation of CD103 + or CD103 -T RM cells by reactivated T CM cells.…”

Balancing Inflammation and Central Nervous System Homeostasis: T Cell Receptor Signaling in Antiviral Brain TRM Formation and Function

“…Although CD8 bT RM generated in a setting of suboptimal TCR stimulation enjoyed a more robust ability to expand upon pathogen reencounter, no impact on effector function was observed. Similarly, Langlois and colleagues reported an advantage in forming influenza-specific lung CD8 T RM after stimulation with low-affinity epitopes ( 12 ). Here, TCR transgenic OT-I CD8 T cells (specific for the H-2K b -restricted SIINFEKL peptide from chicken ovalbumin residues 257–264) were adoptively transferred to mice infected with a recombinant influenza virus encoding native and altered OT-I epitopes.…”

“…The strength of signal transduction events orchestrated after TCR binding with its cognate pMHC regulates induction of transcription factors, tissue-trafficking adhesion molecules, and cytokine receptors required for T RM generation. Thus, TCR signal strength per se dictates the quality and abundance of the resulting T RM population ( 11 , 12 ). Additionally, regulating TCR signaling via inhibitory receptors, such as programmed cell death protein-1 [PD-1(CD279)], may be essential for T RM maintenance in particular tissues by operating as a rheostat to fine tune T cell activation and effector function.…”

Long-term surviving influenza infected cells evade CD8+ T cell mediated clearance

“…PA_Cre was then cloned into pDZ rescue system via In-Fusion HD cloning. NA_GP33 was inserted into the stalk of NA at a position amenable to insertion via infusion cloning as described [39, 40]. All viruses were rescued via HEK293T transfection and amplified in embryonated chicken eggs as previously described [41].…”