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Viral MHCI inhibition evades tissue-resident memory T cell formation and responses.


ABSTRACT: Tissue-resident memory CD8+ T cells (TRMs) confer rapid protection and immunity against viral infections. Many viruses have evolved mechanisms to inhibit MHCI presentation in order to evade CD8+ T cells, suggesting that these mechanisms may also apply to TRM-mediated protection. However, the effects of viral MHCI inhibition on the function and generation of TRMs is unclear. Herein, we demonstrate that viral MHCI inhibition reduces the abundance of CD4+ and CD8+ TRMs, but its effects on the local microenvironment compensate to promote antigen-specific CD8+ TRM formation. Unexpectedly, local cognate antigen enhances CD8+ TRM development even in the context of viral MHCI inhibition and CD8+ T cell evasion, strongly suggesting a role for in situ cross-presentation in local antigen-driven TRM differentiation. However, local cognate antigen is not required for CD8+ TRM maintenance. We also show that viral MHCI inhibition efficiently evades CD8+ TRM effector functions. These findings indicate that viral evasion of MHCI antigen presentation has consequences on the development and response of antiviral TRMs.

SUBMITTER: Lauron EJ 

PROVIDER: S-EPMC6314518 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Viral MHCI inhibition evades tissue-resident memory T cell formation and responses.

Lauron Elvin J EJ   Yang Liping L   Harvey Ian B IB   Sojka Dorothy K DK   Williams Graham D GD   Paley Michael A MA   Bern Michael D MD   Park Eugene E   Victorino Francisco F   Boon Adrianus C M ACM   Yokoyama Wayne M WM  

The Journal of experimental medicine 20181217 1


Tissue-resident memory CD8<sup>+</sup> T cells (T<sub>RM</sub>s) confer rapid protection and immunity against viral infections. Many viruses have evolved mechanisms to inhibit MHCI presentation in order to evade CD8<sup>+</sup> T cells, suggesting that these mechanisms may also apply to T<sub>RM</sub>-mediated protection. However, the effects of viral MHCI inhibition on the function and generation of T<sub>RM</sub>s is unclear. Herein, we demonstrate that viral MHCI inhibition reduces the abunda  ...[more]

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