Cargando…

TCR stimulation strength is inversely associated with establishment of functional brain-resident memory CD8 T cells during persistent viral infection

Establishing functional tissue-resident memory (T(RM)) cells at sites of infection is a newfound objective of T cell vaccine design. To directly assess the impact of antigen stimulation strength on memory CD8 T cell formation and function during a persistent viral infection, we created a library of...

Descripción completa

Detalles Bibliográficos
Autores principales: Maru, Saumya, Jin, Ge, Schell, Todd D., Lukacher, Aron E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406018/
https://www.ncbi.nlm.nih.gov/pubmed/28410427
http://dx.doi.org/10.1371/journal.ppat.1006318
_version_ 1783231883008540672
author Maru, Saumya
Jin, Ge
Schell, Todd D.
Lukacher, Aron E.
author_facet Maru, Saumya
Jin, Ge
Schell, Todd D.
Lukacher, Aron E.
author_sort Maru, Saumya
collection PubMed
description Establishing functional tissue-resident memory (T(RM)) cells at sites of infection is a newfound objective of T cell vaccine design. To directly assess the impact of antigen stimulation strength on memory CD8 T cell formation and function during a persistent viral infection, we created a library of mouse polyomavirus (MuPyV) variants with substitutions in a subdominant CD8 T cell epitope that exhibit a broad range of efficiency in stimulating TCR transgenic CD8 T cells. By altering a subdominant epitope in a nonstructural viral protein and monitoring memory differentiation of donor monoclonal CD8 T cells in immunocompetent mice, we circumvented potentially confounding changes in viral infection levels, virus-associated inflammation, size of the immunodominant virus-specific CD8 T cell response, and shifts in TCR affinity that may accompany temporal recruitment of endogenous polyclonal cells. Using this strategy, we found that antigen stimulation strength was inversely associated with the function of memory CD8 T cells during a persistent viral infection. We further show that CD8 T(RM) cells recruited to the brain following systemic infection with viruses expressing epitopes with suboptimal stimulation strength respond more efficiently to challenge CNS infection with virus expressing cognate antigen. These data demonstrate that the strength of antigenic stimulation during recruitment of CD8 T cells influences the functional integrity of T(RM) cells in a persistent viral infection.
format Online
Article
Text
id pubmed-5406018
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-54060182017-05-14 TCR stimulation strength is inversely associated with establishment of functional brain-resident memory CD8 T cells during persistent viral infection Maru, Saumya Jin, Ge Schell, Todd D. Lukacher, Aron E. PLoS Pathog Research Article Establishing functional tissue-resident memory (T(RM)) cells at sites of infection is a newfound objective of T cell vaccine design. To directly assess the impact of antigen stimulation strength on memory CD8 T cell formation and function during a persistent viral infection, we created a library of mouse polyomavirus (MuPyV) variants with substitutions in a subdominant CD8 T cell epitope that exhibit a broad range of efficiency in stimulating TCR transgenic CD8 T cells. By altering a subdominant epitope in a nonstructural viral protein and monitoring memory differentiation of donor monoclonal CD8 T cells in immunocompetent mice, we circumvented potentially confounding changes in viral infection levels, virus-associated inflammation, size of the immunodominant virus-specific CD8 T cell response, and shifts in TCR affinity that may accompany temporal recruitment of endogenous polyclonal cells. Using this strategy, we found that antigen stimulation strength was inversely associated with the function of memory CD8 T cells during a persistent viral infection. We further show that CD8 T(RM) cells recruited to the brain following systemic infection with viruses expressing epitopes with suboptimal stimulation strength respond more efficiently to challenge CNS infection with virus expressing cognate antigen. These data demonstrate that the strength of antigenic stimulation during recruitment of CD8 T cells influences the functional integrity of T(RM) cells in a persistent viral infection. Public Library of Science 2017-04-14 /pmc/articles/PMC5406018/ /pubmed/28410427 http://dx.doi.org/10.1371/journal.ppat.1006318 Text en © 2017 Maru et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Maru, Saumya
Jin, Ge
Schell, Todd D.
Lukacher, Aron E.
TCR stimulation strength is inversely associated with establishment of functional brain-resident memory CD8 T cells during persistent viral infection
title TCR stimulation strength is inversely associated with establishment of functional brain-resident memory CD8 T cells during persistent viral infection
title_full TCR stimulation strength is inversely associated with establishment of functional brain-resident memory CD8 T cells during persistent viral infection
title_fullStr TCR stimulation strength is inversely associated with establishment of functional brain-resident memory CD8 T cells during persistent viral infection
title_full_unstemmed TCR stimulation strength is inversely associated with establishment of functional brain-resident memory CD8 T cells during persistent viral infection
title_short TCR stimulation strength is inversely associated with establishment of functional brain-resident memory CD8 T cells during persistent viral infection
title_sort tcr stimulation strength is inversely associated with establishment of functional brain-resident memory cd8 t cells during persistent viral infection
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5406018/
https://www.ncbi.nlm.nih.gov/pubmed/28410427
http://dx.doi.org/10.1371/journal.ppat.1006318
work_keys_str_mv AT marusaumya tcrstimulationstrengthisinverselyassociatedwithestablishmentoffunctionalbrainresidentmemorycd8tcellsduringpersistentviralinfection
AT jinge tcrstimulationstrengthisinverselyassociatedwithestablishmentoffunctionalbrainresidentmemorycd8tcellsduringpersistentviralinfection
AT schelltoddd tcrstimulationstrengthisinverselyassociatedwithestablishmentoffunctionalbrainresidentmemorycd8tcellsduringpersistentviralinfection
AT lukacherarone tcrstimulationstrengthisinverselyassociatedwithestablishmentoffunctionalbrainresidentmemorycd8tcellsduringpersistentviralinfection