tetano
Editor, Senior Moderator
Cell
. 2021 Jun 3;S0092-8674(21)00701-7.
doi: 10.1016/j.cell.2021.05.046. Online ahead of print.
Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs
Shira Weingarten-Gabbay[SUP] 1 [/SUP], Susan Klaeger[SUP] 2 [/SUP], Siranush Sarkizova[SUP] 3 [/SUP], Leah R Pearlman[SUP] 3 [/SUP], Da-Yuan Chen[SUP] 4 [/SUP], Kathleen M E Gallagher[SUP] 5 [/SUP], Matthew R Bauer[SUP] 6 [/SUP], Hannah B Taylor[SUP] 3 [/SUP], W Augustine Dunn[SUP] 7 [/SUP], Christina Tarr[SUP] 7 [/SUP], John Sidney[SUP] 8 [/SUP], Suzanna Rachimi[SUP] 3 [/SUP], Hasahn L Conway[SUP] 4 [/SUP], Katelin Katsis[SUP] 9 [/SUP], Yuntong Wang[SUP] 7 [/SUP], Del Leistritz-Edwards[SUP] 7 [/SUP], Melissa R Durkin[SUP] 7 [/SUP], Christopher H Tomkins-Tinch[SUP] 10 [/SUP], Yaara Finkel[SUP] 11 [/SUP], Aharon Nachshon[SUP] 11 [/SUP], Matteo Gentili[SUP] 3 [/SUP], Keith D Rivera[SUP] 3 [/SUP], Isabel P Carulli[SUP] 12 [/SUP], Vipheaviny A Chea[SUP] 12 [/SUP], Abishek Chandrashekar[SUP] 13 [/SUP], Cansu Cimen Bozkus[SUP] 14 [/SUP], Mary Carrington[SUP] 15 [/SUP], MGH COVID-19 Collection & Processing Team; Nina Bhardwaj[SUP] 14 [/SUP], Dan H Barouch[SUP] 16 [/SUP], Alessandro Sette[SUP] 17 [/SUP], Marcela V Maus[SUP] 18 [/SUP], Charles M Rice[SUP] 19 [/SUP], Karl R Clauser[SUP] 3 [/SUP], Derin B Keskin[SUP] 20 [/SUP], Daniel C Pregibon[SUP] 7 [/SUP], Nir Hacohen[SUP] 21 [/SUP], Steven A Carr[SUP] 3 [/SUP], Jennifer G Abelin[SUP] 3 [/SUP], Mohsan Saeed[SUP] 22 [/SUP], Pardis C Sabeti[SUP] 23 [/SUP]
Collaborators, Affiliations
Abstract
T cell-mediated immunity plays an important role in controlling SARS-CoV-2 infection, but the repertoire of naturally processed and presented viral epitopes on class I human leukocyte antigen (HLA-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 open reading frames (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 individuals with COVID-19 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.
Keywords: HLA Class I; SARS-CoV-2; T Cell response; coronavirus; immunogenicity; out-of-frame ORF immunopeptidomics; viral infection.
. 2021 Jun 3;S0092-8674(21)00701-7.
doi: 10.1016/j.cell.2021.05.046. Online ahead of print.
Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs
Shira Weingarten-Gabbay[SUP] 1 [/SUP], Susan Klaeger[SUP] 2 [/SUP], Siranush Sarkizova[SUP] 3 [/SUP], Leah R Pearlman[SUP] 3 [/SUP], Da-Yuan Chen[SUP] 4 [/SUP], Kathleen M E Gallagher[SUP] 5 [/SUP], Matthew R Bauer[SUP] 6 [/SUP], Hannah B Taylor[SUP] 3 [/SUP], W Augustine Dunn[SUP] 7 [/SUP], Christina Tarr[SUP] 7 [/SUP], John Sidney[SUP] 8 [/SUP], Suzanna Rachimi[SUP] 3 [/SUP], Hasahn L Conway[SUP] 4 [/SUP], Katelin Katsis[SUP] 9 [/SUP], Yuntong Wang[SUP] 7 [/SUP], Del Leistritz-Edwards[SUP] 7 [/SUP], Melissa R Durkin[SUP] 7 [/SUP], Christopher H Tomkins-Tinch[SUP] 10 [/SUP], Yaara Finkel[SUP] 11 [/SUP], Aharon Nachshon[SUP] 11 [/SUP], Matteo Gentili[SUP] 3 [/SUP], Keith D Rivera[SUP] 3 [/SUP], Isabel P Carulli[SUP] 12 [/SUP], Vipheaviny A Chea[SUP] 12 [/SUP], Abishek Chandrashekar[SUP] 13 [/SUP], Cansu Cimen Bozkus[SUP] 14 [/SUP], Mary Carrington[SUP] 15 [/SUP], MGH COVID-19 Collection & Processing Team; Nina Bhardwaj[SUP] 14 [/SUP], Dan H Barouch[SUP] 16 [/SUP], Alessandro Sette[SUP] 17 [/SUP], Marcela V Maus[SUP] 18 [/SUP], Charles M Rice[SUP] 19 [/SUP], Karl R Clauser[SUP] 3 [/SUP], Derin B Keskin[SUP] 20 [/SUP], Daniel C Pregibon[SUP] 7 [/SUP], Nir Hacohen[SUP] 21 [/SUP], Steven A Carr[SUP] 3 [/SUP], Jennifer G Abelin[SUP] 3 [/SUP], Mohsan Saeed[SUP] 22 [/SUP], Pardis C Sabeti[SUP] 23 [/SUP]
Collaborators, Affiliations
- PMID: 34171305
- DOI: 10.1016/j.cell.2021.05.046
Abstract
T cell-mediated immunity plays an important role in controlling SARS-CoV-2 infection, but the repertoire of naturally processed and presented viral epitopes on class I human leukocyte antigen (HLA-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 open reading frames (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 individuals with COVID-19 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.
Keywords: HLA Class I; SARS-CoV-2; T Cell response; coronavirus; immunogenicity; out-of-frame ORF immunopeptidomics; viral infection.