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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, William and Xu, Alexander M. and Ng, Alphonsus H. C. and Choi, Jongchan and Xie, Jingyi and Yuan, Dan and Delucia, Diane C. and Edmark, Rick A. and Jones, Lesley C. and Schmitt, Thomas M. and Chaffee, Mary E. and Duvvuri, Venkata R. and Murray, Kim M. and Peng, Songming and Wallick, Julie and Algren, Heather A. and Berrington, William R. and O'Mahoney, D. Shane and Lee, John K. and Greenberg, Philip D. and Goldman, Jason D. and Heath, James R. (2020) Shared Antigen-specific CD8⁺ T cell Responses Against the SARS-COV-2 Spike Protein in HLA A*02:01 COVID-19 Participants. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20201120-071520503

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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.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2020.05.04.20085779DOIDiscussion Paper
ORCID:
AuthorORCID
Chour, William0000-0003-1817-0123
Xu, Alexander M.0000-0003-4877-4358
Ng, Alphonsus H. C.0000-0003-0074-4598
Peng, Songming0000-0002-2742-6584
Lee, John K.0000-0003-4077-0395
Goldman, Jason D.0000-0002-3825-6832
Heath, James R.0000-0001-5356-4385
Alternate Title:Shared Antigen-specific CD8+ T cell Responses Against the SARS-COV-2 Spike Protein in HLA A*02:01 COVID-19 Participants
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.
Group:COVID-19
Funders:
Funding AgencyGrant Number
Parker Institute for Cancer ImmunotherapyUNSPECIFIED
Washington State Andy Hill CARE FoundationUNSPECIFIED
Wilke Family FoundationUNSPECIFIED
M. J. Murdock Charitable TrustUNSPECIFIED
Swedish FoundationUNSPECIFIED
Record Number:CaltechAUTHORS:20201120-071520503
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201120-071520503
Official Citation:Shared Antigen-specific CD8+ T cell Responses Against the SARS-COV-2 Spike Protein in HLA A*02:01 COVID-19 Participants. William Chour, Alex M Xu, Alphonsus H.C. Ng, Jongchan Choi, Jingyi Xie, Dan Yuan, John K. Lee, Diane C. Delucia, Rick Edmark, Lesley Jones, Thomas M. Schmitt, Mary E. Chaffee, Venkata Duvvuri, Philip D. Greenberg, Kim Murray, Julie Wallick, Heather A. Algren, William R. Berrington, D. Shane O'Mahoney, Jason D. Goldman, James R Heath. medRxiv 2020.05.04.20085779; doi: https://doi.org/10.1101/2020.05.04.20085779
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:106749
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:20 Nov 2020 17:25
Last Modified:02 Feb 2021 19:07

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