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

Elvin J. Lauron, Liping Yang, Ian B. Harvey, Dorothy K. Sojka, Graham D. Williams, Michael A. Paley, Michael D. Bern, Eugene Park, Francisco Victorino, Adrianus C.M. Boon, Wayne M. Yokoyama

Research output: Contribution to journalComment/debate

4 Scopus citations

Abstract

Tissue-resident memory CD8 + T cells (T RM s) 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 T RM -mediated protection. However, the effects of viral MHCI inhibition on the function and generation of T RM s is unclear. Herein, we demonstrate that viral MHCI inhibition reduces the abundance of CD4 + and CD8 + T RM s, but its effects on the local microenvironment compensate to promote antigen-specific CD8 + T RM formation. Unexpectedly, local cognate antigen enhances CD8 + T RM 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 T RM differentiation. However, local cognate antigen is not required for CD8 + T RM maintenance. We also show that viral MHCI inhibition efficiently evades CD8 + T RM effector functions. These findings indicate that viral evasion of MHCI antigen presentation has consequences on the development and response of antiviral T RM s.

Original languageEnglish
Pages (from-to)117-132
Number of pages16
JournalJournal of Experimental Medicine
Volume216
Issue number1
DOIs
StatePublished - Jan 1 2019

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