8/18/2023 0 Comments Dna vs rna tcr repertoire![]() ![]() Superantigenic Character of an Insert Unique to SARS-CoV-2 Spike Supported by Skewed TCR Repertoire in Patients with Hyperinflammation. doi: 10.1172/jci.insight.142167.Ĭheng M.H., Zhang S., Porritt R.A., Noval Rivas M., Paschold L., Willscher E., Binder M., Arditi M., Bahar I. High Levels of SARS-CoV-2-Specific T Cells with Restricted Functionality in Severe Courses of COVID-19. Schub D., Klemis V., Schneitler S., Mihm J., Lepper P.M., Wilkens H., Bals R., Eichler H., Gartner B.C., Becker S.L., et al. T Cell Immunity to SARS-CoV-2 Following Natural Infection and Vaccination. T Cell Responses in Patients with COVID-19. Demographic Perspectives on the Mortality of COVID-19 and Other Epidemics. Bulk TCR repertoire sequencing has proven to be a useful and cost-effective approach to understanding interactions between SARS-CoV-2 and the human host, with the potential to inform the design of therapeutics and vaccines, as well as to provide invaluable pathogenetic and epidemiological insights.ĬOVID-19 SARS-CoV-2 T-cell receptor repertoire antibody coronavirus diversity immune response immunological memory immunoreceptor machine learning. Such a superantigen-like activity, which is apparently absent from other coronaviruses, may be the basis of multisystem inflammatory syndrome and cytokine storms in COVID-19. A possible superantigen-like effect of the SARS-CoV-2 spike protein has been identified, by means of observing V-segment skewing in patients with severe COVID-19, together with structural modelling. Closely related clonotypes to these previously identified sequences have been shown to respond with similar kinetics during infection. It has been possible to follow clonotypic sequences longitudinally, which has been particularly valuable for clonotypes known to be associated with SARS-CoV-2 peptide/MHC tetramer binding or with SARS-CoV-2 peptide-induced cytokine responses. TCR repertoire narrowing in severe COVID-19 is most likely a consequence of COVID-19-associated lymphopenia. Maintenance of TCR repertoire diversity, including the maintenance of diversity of anti-SARS-CoV-2 response, predicts a favourable outcome. TCR repertoire sequencing has demonstrated early expansion followed by contraction of SARS-CoV-2-specific clonotypes, during active infection. The complexity of sequencing data obtained by bulk repertoire sequencing makes analysis challenging, but simple descriptive analyses, clonal analysis, searches for specific sequences associated with immune responses to SARS-CoV-2, motif-based analyses, and machine learning approaches have all been applied. The advances in understanding SARS-CoV-2 immunity that have resulted from bulk TCR repertoire sequencing are also be discussed. This review deals with the utility of bulk, rather than single-cell, sequencing of TCR repertoires, considering the importance of study design, in terms of cohort selection, laboratory methods and analysis. Because each T cell carries an essentially unique nucleic acid sequence for its T-cell receptor (TCR), we can interrogate sequence data derived from DNA or RNA to assess aspects of the immune response. Measuring immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 19 (COVID-19), can rely on antibodies, reactive T cells and other factors, with T-cell-mediated responses appearing to have greater sensitivity and longevity. ![]()
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