Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs

ABSTRACT: 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.

INSTRUMENT(S): Orbitrap Exploris 480

ORGANISM(S): Sars Coronavirus (ncbitaxon:227859) Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Steven A. Carr

PROVIDER: MSV000087225 | MassIVE | Sat Apr 17 06:14:00 BST 2021

SECONDARY ACCESSION(S): PXD025449

REPOSITORIES: MassIVE

ACCESS DATA

Json Xml

Similar Datasets

SARS-CoV-2 infected cells present HLA-I peptides from canonical and out-of-frame ORFs

Project description:T cell-mediated immunity seems to play a critical role against SARS-CoV-2 infection and establishing protective memory. Yet the repertoire of viral epitopes responsible for activation of T cell responses remains mostly unknown. Identification and characterization of viral peptides presented on class I human leukocyte antigen (HLA-I) will reveal the viral signatures as seen by cytotoxic T cells that can then be harnessed for the development of effective vaccines. Here, we report the first HLA-I immunopeptidome of SARS-CoV-2 in two human 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 Nucleoprotein not currently captured by vaccine approaches. Whole proteome analysis revealed that expression of ubiquitination pathway proteins, and the proteasome maturation protein, POMP, were significantly altered in infected cells. Retrospective analysis of computational predictions highlighted shortcomings of in silico-only approaches in recovering the observed viral epitopes. Finally, given the experimental evidence for endogenous processing and presentation of the viral peptides we detected, we estimated that at least one HLA-A, -B, or -C allele is covered by at least one peptide for 99% of the population. These biological insights and the list of naturally presented SARS-CoV-2 peptides will facilitate data-driven selection of peptides for immune monitoring and vaccine development.

2020-10-08 | GSE159191 | GEO

SARS-CoV-2 infected cells present HLA-I peptides from canonical and out-of-frame ORFs

Project description:SARS-CoV-2 infected cells present HLA-I peptides from canonical and out-of-frame ORFs

| PRJNA667921 | ENA

The HLA-II immunopeptidome of SARS-CoV-2

Project description:Weingarten-Gabbay S, Chen D, Sarkizova S, Taylor HB, Gentili M, Pearlman LR, Bauer MR, Rice CM, Clauser KR, Hacohen N, Carr SA, Abelin JG, Saeed M, Sabeti PC. 2023. Targeted synthetic vaccines have the potential to transform our response to viral outbreaks; yet the design of these vaccines requires a comprehensive knowledge of viral immunogens, including T-cell epitopes. Having previously mapped the SARS-CoV-2 HLA-I landscape, here we report viral peptides that are naturally processed and loaded onto HLA-II complexes in infected cells. We identified over 500 unique viral peptides from canonical proteins, as well as overlapping internal open reading frames (ORFs), revealing, for the first time, the contribution of internal ORFs to the HLA-II peptide repertoire. Most HLA-II peptides co-localized with the known CD4+ T cell epitopes in COVID-19 patients, including a finding that two reported immunodominant regions in the SARS-CoV-2 membrane protein were formed at the level of HLA-II presentation. We observed that the HLA-I and HLA-II pathways target distinct viral proteins, with the structural proteins accounting for the majority of the HLA-II peptidome and non-structural and non-canonical proteins accounting for the majority of the HLA-I peptidome. These findings suggest that the future vaccines should incorporate multiple viral elements harboring CD4+ and CD8+ T cell epitopes to maximize their effectiveness.

2023-05-15 | MSV000091943 | MassIVE

SARS-CoV-2 escapes CD8 T cell surveillance via mutations in MHC-I restricted epitopes [10x]

Project description:CD8+ T cell immunity to SARS-CoV-2 has been implicated in COVID-19 severity and virus control. Here, we identified non-synonymous mutations in MHC-I restricted CD8+ T cell epitopes after deep sequencing of 747 SARS-CoV-2 virus isolates. Mutant peptides exhibited diminished or abrogated MHC-I binding, which was associated with a loss of recognition and functional responses by CD8+ T cells isolated from HLA-matched COVID-19 patients. Our findings highlight the capacity of SARS-CoV-2 to subvert CD8+ T cell surveillance through sporadically emerging escape mutations in MHC- I restricted viral epitopes.

2021-03-03 | GSE166651 | GEO

The landscape of the SARS-CoV-2 HLA-peptidome

Project description:The human leukocyte antigen (HLA)-bound-viral antigens, serve as an immunological signature that can be selectively recognized by T cells. As viruses evolve by acquiring mutations, it is essential to identify a range of viral presented antigens. Utilizing HLA-peptidomics we Identified SARS-CoV-2-derived peptides presented by highly prevalent HLA Class-I (HLA-I) molecules using infected cells as well as overexpression of SARS-CoV-2 genes. We found 26 HLA-I peptides and 36 HLA class-II (HLA-II) peptides, which are estimated to be presented by at least one HLA allele in 99% of the world population. Among the identified peptides were recurrently presented HLA-I peptides, peptides derived from out-of-frame-ORFs and presentation-hotspots. Seven of these peptides were previously shown to be immunogenic, and we identified two novel immuno-reactive peptides using HLA-multimer staining. These results may aid the development of the next generation of SARS-CoV-2 vaccines based on viral-specific-presented antigens that span several of the viral genes.

2021-06-28 | PXD025499 | Pride

The landscape of the SARS-CoV-2 HLA-peptidome

2021-09-10 | PXD023614 | Pride

TCR repertoire profiling of CMV specific and SARS-CoV2 Spike specific CD8+ T cells using single cell sequencing

Project description:We introduced single-chain trimer (SCT) technologies into a high throughput platform for pMHC library generation that can be used for screening antigen specific CD8+ T cells. We compared the diversity of T cell receptor repertoire captured by SCT and folded peptide-MHC multimer presenting HLA-A02:01 restricted CMV peptide. We then constructed SCT libraries designed to capture SARS-CoV-2 spike specific CD8+ T cells from COVID-19 participants and healthy donors. TCR sequencing with antigen specificity was analyzed. The immunogenicity of these epitopes was validated by functional assays of T cells with cloned TCRs captured using SCT libraries.

2022-01-01 | E-MTAB-11229 | biostudies-arrayexpress

Identification and characterization of a SARS-CoV-2 specific CD8 T cell response with immunodominant features

Project description:The COVID-19 pandemic caused by SARS-CoV-2 is a continuous challenge worldwide, and there is an urgent need to map the landscape of immunogenic and immunodominant epitopes recognized by CD8 T cells. Here, we analyze samples from 31 COVID-19 patients for CD8 T cell recognition of 500 peptide-HLA class I complexes, restricted by 10 common HLA alleles. We identify 18 CD8 T cell recognized SARS-CoV-2 epitopes, including an epitope with immunodominant features derived from ORF1ab and restricted by HLA-A*01:01. In-depth characterization of SARS-CoV-2-specific CD8 T cell responses of patients with acute critical and severe disease reveals high expression of NKG2A, lack of cytokine production and a gene expression profile inhibiting T cell re-activation and migration while sustaining survival. SARS-CoV-2-specific CD8 T cell responses are detectable up to 5 months post recovery from critical and severe disease, and these responses convert from dysfunctional effector to functional memory CD8 T cells during convalescence.

2021-03-25 | GSE169503 | GEO

The landscape of the SARS-CoV-2 HLA-peptidome

2021-11-01 | MSV000088298 | MassIVE

SARS-CoV-2 escapes CD8 T cell surveillance via mutations in MHC-I restricted epitopes [10x]

| EGAS00001005060 | EGA