TY - JOUR
T1 - Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs
AU - MGH COVID-19 Collection & Processing Team
AU - Weingarten-Gabbay, Shira
AU - Klaeger, Susan
AU - Sarkizova, Siranush
AU - Pearlman, Leah R.
AU - Chen, Da Yuan
AU - Gallagher, Kathleen M.E.
AU - Bauer, Matthew R.
AU - Taylor, Hannah B.
AU - Dunn, W. Augustine
AU - Tarr, Christina
AU - Sidney, John
AU - Rachimi, Suzanna
AU - Conway, Hasahn L.
AU - Katsis, Katelin
AU - Wang, Yuntong
AU - Leistritz-Edwards, Del
AU - Durkin, Melissa R.
AU - Tomkins-Tinch, Christopher H.
AU - Finkel, Yaara
AU - Nachshon, Aharon
AU - Gentili, Matteo
AU - Rivera, Keith D.
AU - Carulli, Isabel P.
AU - Chea, Vipheaviny A.
AU - Chandrashekar, Abishek
AU - Bozkus, Cansu Cimen
AU - Carrington, Mary
AU - Lavin-Parsons, Kendall
AU - Parry, Blair
AU - Lilley, Brendan
AU - Lodenstein, Carl
AU - McKaig, Brenna
AU - Charland, Nicole
AU - Khanna, Hargun
AU - Margolin, Justin
AU - Gonye, Anna
AU - Gushterova, Irena
AU - Lasalle, Tom
AU - Sharma, Nihaarika
AU - Russo, Brian C.
AU - Rojas-Lopez, Maricarmen
AU - Sade-Feldman, Moshe
AU - Manakongtreecheep, Kasidet
AU - Tantivit, Jessica
AU - Fisher Thomas, Molly
AU - Bhardwaj, Nina
AU - Barouch, Dan H.
AU - Sette, Alessandro
AU - Maus, Marcela V.
AU - Rice, Charles M.
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/7/22
Y1 - 2021/7/22
N2 - 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.
AB - 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.
KW - HLA Class I
KW - SARS-CoV-2
KW - T Cell response
KW - coronavirus
KW - immunogenicity
KW - out-of-frame ORF immunopeptidomics
KW - viral infection
UR - http://www.scopus.com/inward/record.url?scp=85108704604&partnerID=8YFLogxK
U2 - 10.1016/j.cell.2021.05.046
DO - 10.1016/j.cell.2021.05.046
M3 - Article
AN - SCOPUS:85108704604
SN - 0092-8674
VL - 184
SP - 3962-3980.e17
JO - Cell
JF - Cell
IS - 15
ER -