Quantitative Annotations of T-Cell Repertoire Specificity
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Link to bioRxiv paper: http://biorxiv.org/cgi/content/short/2023.01.29.526145v1?rss=1

Authors: Luo, J., Wang, X., Zou, Y., Chen, L., Liu, W., Zhang, W., Li, S.

Abstract: The specificity of a T-cell receptor (TCR) repertoire determines personalized immune capacity. Existing methods have modelled the qualitative aspects of TCR specificity, while the quantitative aspects remained unaddressed. We developed a package, TCRanno, to quantify the specificity of TCR repertoires. Applying TCRanno to 4,195 TCR repertoires revealed quantitative changes in repertoire specificity upon infections, autoimmunity and cancers. Specifically, TCRanno found cytomegalovirus-specific TCRs in seronegative healthy individuals, indicating their past abortive infections instead of non-exposure to the virus. TCRanno discovered age-accumulated SARS-CoV2 specific TCRs in pre-pandemic samples, which may explain the aggressive symptoms and age-related severity of COVID-19. TCRanno also identified the encounter of Hepatitis B antigens as a trigger of systemic lupus erythematosus. TCRanno annotations showed capability in distinguishing TCR repertoires of healthy and cancers including melanoma, lung and breast cancers. TCRanno also demonstrated usefulness to single-cell TCRseq+gene expression data analyses by isolating T-cells with the specificity of interest.

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