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Shared Antigen-specific CD8+ T cell Responses Against the SARS-COV-2 Spike Protein in HLA A*02:01 COVID-19 Participants

Chour, W.; Xu, A. M.; Ng, A. H. C.; Choi, J.; Xie, J.; Yuan, D.; Lee, J. K.; Delucia, D. C.; Edmark, R.; Jones, L.; Schmitt, T. M.; Chaffee, M. E.; Duvvuri, V.; Greenberg, P. D.; Murray, K.; Wallick, J.; Algren, H. A.; Berrington, W. R.; O'Mahoney, D. S.; Goldman, J. D.; Heath, J. R.

2020-05-08 infectious diseases
10.1101/2020.05.04.20085779 medRxiv
Show abstract

We report here on antigens from the SARS-CoV-2 virus spike protein, that when presented by Class I MHC, can lead to cytotoxic CD8+ T cell anti-viral responses in COVID-19 patients. We present a method in which the SARS-CoV-2 spike protein is converted into a library of peptide antigen-Major Histocompatibility Complexes (pMHCs) as single chain trimers that contain the peptide antigen, the MHC HLA allele subunit, and the {beta}-2 microglobulin subunit. This library is used to detect the evolution of virus-specific T cell populations in four COVID-19 study participants two of which share one HLA allele, and the other two a second HLA allele, at two time points over the initial course of infection. HLA-matched participants exhibit similar virus-specific T cell populations, but very different time-trajectories of those populations. This strategy can be used to track those virus-specific T cell populations over the course of an infection, thus providing deep insight into the SARS-CoV-2 immune system trajectories observed in different COVID-19 patients.

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