Antibodies are only half of the story of acquired immunity to viral infections. CD8+ T cells recognize and kill infected host cells, while CD4+ T cells instruct and coordinate the host immune response. Grifoni et al. characterized the CD4+ and CD8+ T cell responses to SARS-CoV-2 peptides in circulating white blood cells (PBMCs) of 20 convalescing patients with COVID-19. All patients had CD4+ T cells, and 70% had CD8+ cells, that responded to the SARS-CoV-2 antigens tested. More surprisingly, when the authors stimulated PBMCs from 11 healthy control participants collected between 2015 and 2018, approximately half of the samples showed cross-reactive activation of CD4+ T cells by SARS-CoV-2 antigens. The authors also detected cross-reactivity in CD8+ T cells, although this was less strong and less frequent. Pre-existing cross-reactive immunity of both T cells and B cells to SARS-CoV-2 antigens has since been demonstrated by several groups, although its importance, if any, remains unclear. TC https://doi. org/10.1038/s41591-020-01161-0