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- W4313383553 abstract "Abstract T cell receptor (TCR) rearrangement results in germ-line editing of a T cell’s TCR loci. During infection, T cells with TCRs specific for the pathogen proliferate. Resulting pathogen-specific memory T cells retain the unique germ-line TCR DNA rearrangements, which we hypothesized may be used as molecular biomarkers of prior pathogen exposure. We performed high-throughput sequencing of the TCRβ repertoires of HLA-A2 transgenic mice pre- and post- inoculation with either the smallpox vaccine or highly-related monkeypox virus (MPXV). We generated a database of >2×106 unique TCRβ clonotypes from samples pre- (naïve) and post-exposure to identify TCRs associated with vaccinated/infected samples vs naïve in 58 individual mice. We computationally identified 315 TCRβ sequences statistically associated with post-vaccinated samples, which we used to develop a diagnostic assay to classify samples as naïve or previously-exposed with 97% accuracy up to 9-months post-vaccination. We validated this assay in an independent cohort of MPXV infected mice. The diagnostic platform was adapted to analyze human TCR sequences to distinguish smallpox vaccinated or non-vaccinated individuals. We identified 239 vaccine-associated TCRβ sequences significantly expanded in 100 smallpox vaccinated individuals. A machine learning algorithm was developed to determine individuals’ vaccination status based on the presence of these 239 TCR sequences. Overall, the diagnostic assay correctly identified 74% of non-vaccinated samples and 85% of vaccinated samples. Thus, the analyses support that computational identification of pathogen-associated TCRs is a highly sensitive and specific method for determining prior exposure to an agent or pathogen." @default.
- W4313383553 created "2023-01-06" @default.
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- W4313383553 date "2018-05-01" @default.
- W4313383553 modified "2023-09-27" @default.
- W4313383553 title "Diagnostic Assessment of Immunological History by High-throughput TCR sequence Analyses." @default.
- W4313383553 doi "https://doi.org/10.4049/jimmunol.200.supp.120.4" @default.
- W4313383553 hasPublicationYear "2018" @default.
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