This preprint identifies 1,739 and 1,591 SARS-CoV-2-derived peptides that bind to HLA-A/B/C or HLA-DR, respectively, from 180 SARS-CoV-2 convalescent donors and 185 healthy controls. Nelde et al. show that convalescent donors have T cell responses to multiple SARS-CoV-2 epitopes, with a predominant IFNγ+CD8+ T cell response to HLA-A/B/C-binding peptides but a multifunctional (IFNγ+TNF+CD107a+) CD4+ T cell response to HLA-DR-binding peptides. Some donors had T cell responses but not antibodies, which highlights the potential importance of T cells in COVID-19 vaccine development. IgG responses were associated with severe cases, whereas those with diverse T cell responses had milder disease. Cross-reactive T cell responses to 31% of HLA-A/B/C-binding epitopes and to 70% of HLA-DR-binding epitopes were detected in unexposed individuals, supporting the potential existence of heterologous immunity.