Details

Autor(en) / Beteiligte

• Lineburg, Katie E.
• Grant, Emma J.
• Swaminathan, Srividhya
• Chatzileontiadou, Demetra S.M.
• Szeto, Christopher
• Sloane, Hannah
• Panikkar, Archana
• Raju, Jyothy
• Crooks, Pauline
• Rehan, Sweera
• Nguyen, Andrea T.
• Lekieffre, Lea
• Neller, Michelle A.
• Tong, Zhen Wei Marcus
• Jayasinghe, Dhilshan
• Chew, Keng Yih
• Lobos, Christian A.
• Halim, Hanim
• Burrows, Jacqueline M.
• Riboldi-Tunnicliffe, Alan
• Chen, Weisan
• D’Orsogna, Lloyd
• Khanna, Rajiv
• Short, Kirsty R.
• Smith, Corey
• Gras, Stephanie

Titel

CD8+ T cells specific for an immunodominant SARS-CoV-2 nucleocapsid epitope cross-react with selective seasonal coronaviruses

Ist Teil von

• Immunity (Cambridge, Mass.), 2021-05, Vol.54 (5), p.1055-1065.e5

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] •ICS assay detects SARS-CoV-2-specific T cells in unexposed and recovered donors•Epitope mapping identifies one dominant HLA-B7-restricted epitope•Identical TCR clonotypes recognize SARS-CoV-2 and betacoronaviruses epitopes•Crystal structures reveal distinct peptide conformations between alpha- and betacoronaviruses The impact of seasonal coronaviruses on immune responses to SARS-CoV-2 is an active area of research. Lineburg et al. identify CD8+ T cells specific for a conserved and immunodominant SARS-CoV-2 epitope in HLA-B7+ individuals. Furthermore, SARS-CoV-2 epitope-specific CD8+ T cells display cross-reactivity to beta- but not alphacoronaviruses because of distinct peptide-HLA conformations.