PT  - JOURNAL ARTICLE
AU  - Jun Siong Low
AU  - Daniela Vaqueirinho
AU  - Federico Mele
AU  - Mathilde Foglierini
AU  - Michela Perotti
AU  - David Jarrossay
AU  - Sandra Jovic
AU  - Tatiana Terrot
AU  - Alessandra Franzetti Pellanda
AU  - Maira Biggiogero
AU  - Christian Garzoni
AU  - Paolo Ferrari
AU  - Alessandro Ceschi
AU  - Antonio Lanzavecchia
AU  - Antonino Cassotta
AU  - Federica Sallusto
TI  - Clonal dissection of immunodominance and cross-reactivity of the CD4<sup>+</sup> T cell response to SARS-CoV-2
AID  - 10.1101/2021.03.23.436642
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.03.23.436642
4099  - http://biorxiv.org/content/early/2021/03/23/2021.03.23.436642.short
4100  - http://biorxiv.org/content/early/2021/03/23/2021.03.23.436642.full
AB  - The identification of CD4+ T cell epitopes is essential for the design of effective vaccines capable of inducing neutralizing antibodies and long-term immunity. Here we demonstrate in COVID-19 patients a robust CD4+ T cell response to naturally processed SARS-CoV-2 Spike and Nucleoprotein, including effector, helper and memory T cells. By characterizing 2,943 Spike-reactive T cell clones, we found that 34% of the clones and 93% of the patients recognized a conserved immunodominant region encompassing residues S346-365 in the RBD and comprising three nested HLA-DR and HLA-DP restricted epitopes. By using pre- and post-COVID-19 samples and Spike proteins from alpha and beta coronaviruses, we provide in vivo evidence of cross-reactive T cell responses targeting multiple sites in the SARS-CoV-2 Spike protein. The possibility of leveraging immunodominant and cross-reactive T helper epitopes is instrumental for vaccination strategies that can be rapidly adapted to counteract emerging SARS-CoV-2 variants.Competing Interest StatementThe authors have declared no competing interest.