PXD025449

PXD025449 is an original dataset announced via ProteomeXchange.

Title	Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs
Description	Weingarten-Gabbay S, Klaeger S, Sarkizova S, Pearlman LR, Chen D, Gallagher K, Bauer MR, Taylor HB, W. Augustine Dunn WA, Tarr C, Sidney J, Rachimi S, Conway HL, Katsis K, Yuntong Wang Y, Leistritz-Edwards D, Durkin MR, Tomkins-Tinch CH, Finkel Y, Nachshon A, Gentili M, Rivera KD, Carulli IP, Chea VA, Chandrashekar A, Bozkus CC, Carrington M, MGH COVID-19 Collection & Processing Team, Bhardwaj N, Barouch DH, Sette A, Maus MV, Rice CM, Clauser KR, Keskin DB, Pregibon DC, Hacohen N, Carr SA, Abelin JG, Saeed M, Sabeti PC. 2021 T cell-mediated immunity plays an important role in controlling SARS-CoV-2 infection; yet the repertoire of naturally processed and presented viral epitopes on HLA class I remains uncharacterized. Here, we report the first HLA-I immunopeptidome of SARS-CoV-2 in two cell lines at different times post-infection using mass spectrometry. We found HLA-I peptides derived not only from canonical ORFs, but also from internal out-of-frame ORFs in Spike and Nucleocapsid not captured by current vaccines. Some peptides from out-of-frame ORFs elicited T cell responses in a humanized mouse model and COVID-19 patients that exceeded responses to canonical peptides including some of the strongest epitopes reported to date. Whole proteome analysis of infected cells revealed that early expressed viral proteins contribute more to HLA-I presentation and immunogenicity. These biological insights as well as the discovery of out-of-frame ORF epitopes will facilitate selection of peptides for immune monitoring and vaccine development.
HostingRepository	MassIVE
AnnounceDate	2021-06-03
AnnouncementXML	Submission_2021-06-03_06:10:44.112.xml
DigitalObjectIdentifier
ReviewLevel	Non peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Karl Clauser
SpeciesList	scientific name: Homo sapiens; common name: human; NCBI TaxID: 9606; scientific name: SARS coronavirus; NCBI TaxID: 227859;
ModificationList	unknown modification; unknown modification; unknown modification; unknown modification; unknown modification
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2021-04-17 06:14:12	ID requested
⏵ 1	2021-06-03 06:10:44	announced

no publication

submitter keyword: SARS-CoV-2, immunopeptidomics, non-canonical ORFs, TMT

Steven A. Carr
contact affiliation	Broad Institute of MIT and Harvard
contact email	scarr@broadinstitute.org
lab head
Karl Clauser
contact affiliation	Broad Institute of MIT and Harvard
contact email	clauser@broadinstitute.org
dataset submitter

MassIVE dataset URI

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