The impact of TCR signal strength on resident memory T cell formation during influenza virus infection

Jessica K. Fiege; Ian A. Stone; Elizabeth J. Fay; Matthew W. Markman; Sathi Wijeyesinghe; Marissa Macchietto; Steven Shen; David Masopust; Ryan A Langlois

doi:10.4049/jimmunol.1900093

The impact of TCR signal strength on resident memory T cell formation during influenza virus infection

Jessica K. Fiege, Ian A. Stone, Elizabeth J. Fay, Matthew W. Markman, Sathi Wijeyesinghe, Marissa Macchietto, Steven Shen, David Masopust, Ryan A Langlois

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

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.

Original language	English (US)
Pages (from-to)	936-945
Number of pages	10
Journal	Journal of Immunology
Volume	203
Issue number	4
DOIs	https://doi.org/10.4049/jimmunol.1900093
State	Published - Aug 15 2019

Bibliographical note

Funding 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.

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title = "The impact of TCR signal strength on resident memory T cell formation during influenza virus infection",

abstract = "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.",

author = "Fiege, {Jessica K.} and Stone, {Ian A.} and Fay, {Elizabeth J.} and Markman, {Matthew W.} and Sathi Wijeyesinghe and Marissa Macchietto and Steven Shen and David Masopust and Langlois, {Ryan A}",

note = "Funding 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.",

year = "2019",

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doi = "10.4049/jimmunol.1900093",

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AU - Macchietto, Marissa

AU - Shen, Steven

AU - Masopust, David

AU - Langlois, Ryan A

N1 - Funding 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.

PY - 2019/8/15

Y1 - 2019/8/15

N2 - 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.

AB - 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.

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The impact of TCR signal strength on resident memory T cell formation during influenza virus infection

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The impact of TCR signal strength on resident memory T cell formation during influenza virus infection

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