2021
DOI: 10.3389/fimmu.2021.746986
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Cross-Reactivity to Mutated Viral Immune Targets Can Influence CD8+ T Cell Functionality: An Alternative Viral Adaptation Strategy

Abstract: Loss of T cell immunogenicity due to mutations in virally encoded epitopes is a well-described adaptation strategy to limit host anti-viral immunity. Another described, but less understood, adaptation strategy involves the selection of mutations within epitopes that retain immune recognition, suggesting a benefit for the virus despite continued immune pressure (termed non-classical adaptation). To understand this adaptation strategy, we utilized a single cell transcriptomic approach to identify features of the… Show more

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Cited by 6 publications
(3 citation statements)
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“…This site lies within the immunodominant HLA-B � 07-associated GL9 (GP_HKARVL, S3G) epitope and is a known adaptation site previously described to result in a high-avidity CTL response, driving cells to exhaustion [17,35,36]. Subject WA9, who carries HLA-B � 07, also responded to the adapted form of the epitope (S1 Fig), in keeping with previous studies demonstrating maintained or increased recognition of the adapted immunodominant GL9 epitope as an alternative viral adaptation mechanism [36,37].…”
Section: Longitudinal Case Study Of Acute-stage Infection Reveals a T...supporting
confidence: 86%
See 1 more Smart Citation
“…This site lies within the immunodominant HLA-B � 07-associated GL9 (GP_HKARVL, S3G) epitope and is a known adaptation site previously described to result in a high-avidity CTL response, driving cells to exhaustion [17,35,36]. Subject WA9, who carries HLA-B � 07, also responded to the adapted form of the epitope (S1 Fig), in keeping with previous studies demonstrating maintained or increased recognition of the adapted immunodominant GL9 epitope as an alternative viral adaptation mechanism [36,37].…”
Section: Longitudinal Case Study Of Acute-stage Infection Reveals a T...supporting
confidence: 86%
“…For example, inclusion of epitopes where the mutational barrier to escape is predicted to be high and of significant replicative importance (S2 and S3 Tables) may improve HIV control. Alternatively, avoiding regions with common escape variants may reduce immune priming towards subdominant epitopes or immune exhaustion [37]. Ultimately, a greater understanding of early viral adaptation will elucidate patterns of evolution at the population level and enhance approaches for preventative and therapeutic vaccine development.…”
Section: Plos Pathogensmentioning
confidence: 99%
“…Single cell TCR and RNA sequencing was performed on samples from four subjects. Sequencing methodology was as previously described ( 63 ). Briefly, single sorted cells underwent cDNA conversion with indexed well-specific primers followed by a first round PCR with barcoded IS cDNA Amp primers.…”
Section: Methodsmentioning
confidence: 99%