P51 – Role of T cell cross-reactivity in the control of COVID-19

4. Immunologi

Marion Humbert1, Anna Olofsson1, David Wullimann2, Julia Niessl2, Emma Hodcroft3, Ebba Sohlberg2, Yu Gao2, André Pérez Potti2, Robert Dyrdak4, Jan Albert4, Karl-Johan Malmberg2, Richard Neher3, Hans-Gustaf Ljunggren2, Marcus Buggert2, Annika Karlsson1

1 Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden
2 Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden
3 Biozentrum, Basel, Switzerland
4 Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden

Bakgrund: Several studies have demonstrated the presence of T cells recognizing SARS-CoV-2 peptides in unexposed individuals. Mapping of cross-reactive SARS-CoV-2 epitopes revealed pre-existing T cell immunity, potentially induced by seasonal common cold coronaviruses (HCoVs). Our goal was to understand the role of SARS-CoV-2-specific memory T cell responses in relation to previous exposure to HCoVs.

Metod: We created a consensus HCoV-OC43 sequence for the Spike (S), Membrane (M) and Nucleocapsid (N) protein regions. The peptides (20-mer, overlapping by 10) were combined into 3 mega pools and 29 peptide matrix pools, for the identification of individual peptide responses. We also created peptide megapools (S, M and N) and 28 peptide matrix pools corresponding to SARS-CoV-2 SWE/01/2020.The mapping of individual SARS-CoV-2- and OC43-specific T cell responses was performed by FluoroSpot assay (IFN-g), using PBMCs from healthy donor blood collected pre- and post-COVID-19, stimulated for 24 hours with megapools, matrix pools or subsequently identified individual peptides.

Resultat: In blood donor cells obtained during the fall of 2020 (post-COVID-19), we were able to detect positive responses against the S-OC43 and N-OC43 regions in 26 out of 30 subjects (Figure 1A). Responses against M-OC43 were modest, with a positive response detected in 11 out of 30 individuals. Compared to the prevalence of SARS-CoV-2-specific T cell responses in 28% of Swedish blood donors pre-COVID-19, we now detect S-SARS-CoV-2-specific T cells in 50% of our healthy blood donors (Figure 1B).

Slutsats: The results from the matrix pools allowed the identification of immunodominant epitopes for SARS-CoV-2- and OC43-specific T cell responses.