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J Exp Med. 2019 Jan 7;216(1):117-132. doi: 10.1084/jem.20181077. Epub 2018 Dec 17.

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

Author information

1
Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO.
2
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO.
3
Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO.
4
Division of Rheumatology, Department of Medicine, Washington University School of Medicine, St. Louis, MO yokoyama@wustl.edu.

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.

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