TY - JOUR
T1 - CD8+ T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope cross-react with selective seasonal coronaviruses
AU - Lineburg, Katie E.
AU - Grant, Emma J.
AU - Swaminathan, Srividhya
AU - Chatzileontiadou, Demetra S.M.
AU - Szeto, Christopher
AU - Sloane, Hannah
AU - Panikkar, Archana
AU - Raju, Jyothy
AU - Crooks, Pauline
AU - Rehan, Sweera
AU - Nguyen, Andrea T.
AU - Lekieffre, Lea
AU - Neller, Michelle A.
AU - Tong, Zhen Wei Marcus
AU - Jayasinghe, Dhilshan
AU - Chew, Keng Yih
AU - Lobos, Christian A.
AU - Halim, Hanim
AU - Burrows, Jacqueline M.
AU - Riboldi-Tunnicliffe, Alan
AU - Chen, Weisan
AU - D'Orsogna, Lloyd
AU - Khanna, Rajiv
AU - Short, Kirsty R.
AU - Smith, Corey
AU - Gras, Stephanie
PY - 2021/5/11
Y1 - 2021/5/11
N2 - Efforts are being made worldwide to understand the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, including the impact of T cell immunity and cross-recognition with seasonal coronaviruses. Screening of SARS-CoV-2 peptide pools revealed that the nucleocapsid (N) protein induced an immunodominant response in HLA-B7+ COVID-19-recovered individuals that was also detectable in unexposed donors. A single N-encoded epitope that was highly conserved across circulating coronaviruses drove this immunodominant response. In vitro peptide stimulation and crystal structure analyses revealed T cell-mediated cross-reactivity toward circulating OC43 and HKU-1 betacoronaviruses but not 229E or NL63 alphacoronaviruses because of different peptide conformations. T cell receptor (TCR) sequencing indicated that cross-reactivity was driven by private TCR repertoires with a bias for TRBV27 and a long CDR3β loop. Our findings demonstrate the basis of selective T cell cross-reactivity for an immunodominant SARS-CoV-2 epitope and its homologs from seasonal coronaviruses, suggesting long-lasting protective immunity.
AB - Efforts are being made worldwide to understand the immune response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for the coronavirus disease 2019 (COVID-19) pandemic, including the impact of T cell immunity and cross-recognition with seasonal coronaviruses. Screening of SARS-CoV-2 peptide pools revealed that the nucleocapsid (N) protein induced an immunodominant response in HLA-B7+ COVID-19-recovered individuals that was also detectable in unexposed donors. A single N-encoded epitope that was highly conserved across circulating coronaviruses drove this immunodominant response. In vitro peptide stimulation and crystal structure analyses revealed T cell-mediated cross-reactivity toward circulating OC43 and HKU-1 betacoronaviruses but not 229E or NL63 alphacoronaviruses because of different peptide conformations. T cell receptor (TCR) sequencing indicated that cross-reactivity was driven by private TCR repertoires with a bias for TRBV27 and a long CDR3β loop. Our findings demonstrate the basis of selective T cell cross-reactivity for an immunodominant SARS-CoV-2 epitope and its homologs from seasonal coronaviruses, suggesting long-lasting protective immunity.
KW - CD8 T cell
KW - cross-reactivity
KW - HLA
KW - immune response
KW - immunodominant epitope
KW - SARS-CoV-2
KW - seasonal coronaviruses
UR - http://www.scopus.com/inward/record.url?scp=85105337637&partnerID=8YFLogxK
U2 - 10.1016/j.immuni.2021.04.006
DO - 10.1016/j.immuni.2021.04.006
M3 - Article
C2 - 33945786
AN - SCOPUS:85105337637
SN - 1074-7613
VL - 54
SP - 1055-1065.e5
JO - Immunity
JF - Immunity
IS - 5
ER -
