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

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.

Source: The Journal of Experimental Medicine - January 7, 2019 Category: Internal Medicine Authors: Lauron, E. J., Yang, L., Harvey, I. B., Sojka, D. K., Williams, G. D., Paley, M. A., Bern, M. D., Park, E., Victorino, F., Boon, A. C. M., Yokoyama, W. M. Tags: Infectious Disease and Host Defense Articles Source Type: research