tetano
Editor, Senior Moderator
Science
. 2021 May 18;eabg8985.
doi: 10.1126/science.abg8985. Online ahead of print.
Clonal analysis of immunodominance and cross-reactivity of the CD4 T cell response to SARS-CoV-2
Jun Siong Low[SUP] #[/SUP][SUP] 1 [/SUP], Daniela Vaqueirinho[SUP] #[/SUP][SUP] 1 [/SUP], Federico Mele[SUP] #[/SUP][SUP] 1 [/SUP], Mathilde Foglierini[SUP] 1 [/SUP], Josipa Jerak[SUP] 1 [/SUP], Michela Perotti[SUP] 1 [/SUP], David Jarrossay[SUP] 1 [/SUP], Sandra Jovic[SUP] 1 [/SUP], Laurent Perez[SUP] 1 [/SUP], Rosalia Cacciatore[SUP] 2 [/SUP], Tatiana Terrot[SUP] 3 [/SUP], Alessandra Franzetti Pellanda[SUP] 4 [/SUP], Maira Biggiogero[SUP] 4 [/SUP], Christian Garzoni[SUP] 4 [/SUP], Paolo Ferrari[SUP] 5 6 7 [/SUP], Alessandro Ceschi[SUP] 3 5 8 9 [/SUP], Antonio Lanzavecchia[SUP] 10 [/SUP], Federica Sallusto[SUP] #[/SUP][SUP] 11 12 [/SUP], Antonino Cassotta[SUP] #[/SUP][SUP] 11 [/SUP]
Affiliations
Abstract
The identification of CD4[SUP]+[/SUP] T cell epitopes is instrumental for the design of subunit vaccines for broad protection against coronaviruses. Here we demonstrate in COVID-19-recovered individuals a robust CD4[SUP]+[/SUP] T cell response to naturally processed SARS-CoV-2 spike (S) and nucleoprotein (N), including effector, helper, and memory T cells. By characterizing 2943 S-reactive T cell clones from 34 individuals, we found that 34% of clones and 93% of individuals recognized a conserved immunodominant S346-365 region within the RBD comprising nested HLA-DR- and HLA-DP-restricted epitopes. Using pre- and post-COVID-19 samples and S proteins from endemic coronaviruses, we identify cross-reactive T cells targeting multiple S protein sites. The immunodominant and cross-reactive epitopes identified can inform vaccination strategies to counteract emerging SARS-CoV-2 variants.
. 2021 May 18;eabg8985.
doi: 10.1126/science.abg8985. Online ahead of print.
Clonal analysis of immunodominance and cross-reactivity of the CD4 T cell response to SARS-CoV-2
Jun Siong Low[SUP] #[/SUP][SUP] 1 [/SUP], Daniela Vaqueirinho[SUP] #[/SUP][SUP] 1 [/SUP], Federico Mele[SUP] #[/SUP][SUP] 1 [/SUP], Mathilde Foglierini[SUP] 1 [/SUP], Josipa Jerak[SUP] 1 [/SUP], Michela Perotti[SUP] 1 [/SUP], David Jarrossay[SUP] 1 [/SUP], Sandra Jovic[SUP] 1 [/SUP], Laurent Perez[SUP] 1 [/SUP], Rosalia Cacciatore[SUP] 2 [/SUP], Tatiana Terrot[SUP] 3 [/SUP], Alessandra Franzetti Pellanda[SUP] 4 [/SUP], Maira Biggiogero[SUP] 4 [/SUP], Christian Garzoni[SUP] 4 [/SUP], Paolo Ferrari[SUP] 5 6 7 [/SUP], Alessandro Ceschi[SUP] 3 5 8 9 [/SUP], Antonio Lanzavecchia[SUP] 10 [/SUP], Federica Sallusto[SUP] #[/SUP][SUP] 11 12 [/SUP], Antonino Cassotta[SUP] #[/SUP][SUP] 11 [/SUP]
Affiliations
- PMID: 34006597
- DOI: 10.1126/science.abg8985
Abstract
The identification of CD4[SUP]+[/SUP] T cell epitopes is instrumental for the design of subunit vaccines for broad protection against coronaviruses. Here we demonstrate in COVID-19-recovered individuals a robust CD4[SUP]+[/SUP] T cell response to naturally processed SARS-CoV-2 spike (S) and nucleoprotein (N), including effector, helper, and memory T cells. By characterizing 2943 S-reactive T cell clones from 34 individuals, we found that 34% of clones and 93% of individuals recognized a conserved immunodominant S346-365 region within the RBD comprising nested HLA-DR- and HLA-DP-restricted epitopes. Using pre- and post-COVID-19 samples and S proteins from endemic coronaviruses, we identify cross-reactive T cells targeting multiple S protein sites. The immunodominant and cross-reactive epitopes identified can inform vaccination strategies to counteract emerging SARS-CoV-2 variants.