Shared Antigen-specific CD8⁺ T cell Responses Against the SARS-COV-2 Spike Protein in HLA A*02:01 COVID-19 Participants
- Creators
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Chour, William
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Xu, Alexander M.
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Ng, Alphonsus H. C.
- Choi, Jongchan
- Xie, Jingyi
- Yuan, Dan
- Delucia, Diane C.
- Edmark, Rick A.
- Jones, Lesley C.
- Schmitt, Thomas M.
- Chaffee, Mary E.
- Duvvuri, Venkata R.
- Murray, Kim M.
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Peng, Songming
- Wallick, Julie
- Algren, Heather A.
- Berrington, William R.
- O'Mahoney, D. Shane
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Lee, John K.
- Greenberg, Philip D.
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Goldman, Jason D.
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Heath, James R.
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, and the β-2 microglobulin sub-unit. That library is used to detect the evolution of virus-specific T cell populations from two COVID-19 patients, at two time points over the course of infection. Both patients exhibit similar virus-specific T cell populations, but very different time-trajectories of those populations. These results can be used to track those virus-specific T cell populations over the course of an infection, thus providing deep insight into the variations in immune system trajectories observed in different COVID-19 patients.
Additional Information
The copyright holder for this preprint is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. This version posted May 8, 2020. We acknowledge the Parker Institute for Cancer Immunotherapy, the WA State Andy Hill CARE Foundation, the Wilke Foundation, the M.J. Murdock Charitable Trust, and the Swedish Foundation for generous support of this work. Data Availability: Please contact the ISB data manager for release of data. Competing Interest Statement: JRH is a founder and board member of PACT Pharma, which is seeking to commercialize certain of the technologies described here. Author Declarations: All relevant ethical guidelines have been followed; any necessary IRB and/or ethics committee approvals have been obtained and details of the IRB/oversight body are included in the manuscript. Yes. All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes. I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes. I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes.Attached Files
Submitted - 2020.05.04.20085779v1.full.pdf
Supplemental Material - 2020.05.04.20085779-1.pdf
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Additional details
- Alternative title
- Shared Antigen-specific CD8+ T cell Responses Against the SARS-COV-2 Spike Protein in HLA A*02:01 COVID-19 Participants
- Eprint ID
- 106749
- Resolver ID
- CaltechAUTHORS:20201120-071520503
- Parker Institute for Cancer Immunotherapy
- Washington State Andy Hill CARE Foundation
- Wilke Family Foundation
- M. J. Murdock Charitable Trust
- Swedish Foundation
- Created
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2020-11-20Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field
- Caltech groups
- COVID-19