1. Functional analyses and single cell immunoprofiling uncover sex-specific differences in SARS-CoV2 immune memory development
- Author
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Basak Eraslan, Eric Brown, Maura Benson, Liat Amir-Zilberstein, Sung-Moo Park, Betsabeh Tusi, Vladislav Pokatayev, Cody Hecht, Novalia Pishesha, Devan Phillips, Andy Kim, Shuting Zhang, Anthony Gaca, Fadi Ghantous, Toni Delorey, Jonathan Livny, Lindsey Baden, Orit Rozenblatt-Rosen, Daniel Graham, Aviv Regev, Michael Seaman, Ann Woolley, Lisa Cosimi, Deborah Hung, Jacques Deguine, and Ramnik Xavier
- Abstract
SARS-CoV-2 infection leads to a broad range of outcomes and immune responses, with the development of neutralizing antibodies generally correlated with protection against reinfection. Here, we have characterized both neutralizing activity and T cell responses in a cluster of subjects with mild disease linked to a single spreading event. Surprisingly, we observed sex-specific associations between spike- and particularly nucleoprotein-specific T cell responses and neutralization, with pro-inflammatory cytokines being linked to higher titers only in males. Using single cell immunoprofiling, which provided matched transcriptome and T-cell receptor (TCR) profiles in restimulated CD4 + and CD8 + cells from these subjects, we identified differences in type I IFN signaling that may underlie this difference in antibody generation. Finally, we also identified several TCRs associated with cytokine producing T cells. Altogether, our work maps the breadth of immunological outcomes of SARS-CoV2 infections and highlight the potential role of sex-specific feedback loops during the generation of neutralizing antibodies.
- Published
- 2022