Reykjavik UniversityOlafsdottir, Thorunn ABjarnadottir, KristbjorgNorddahl, Gudmundur L.Halldórsson, Gísli HreinnMelsted, PállGunnarsdottir, KristbjorgIvarsdottir, ErnaOlafsdottir, ThorhildurArnthorsson, Asgeir OTheódórs, FannarEyþórsson, Elías SæbjörnHelgason, DadiEggertsson, Hannes P.Masson, GisliBjarnadottir, SolveigSævarsdóttir, SædísRunólfsdóttir, Hrafnhildur L.Ólafsson, ÍsleifurSaemundsdottir, JonaSigurðsson, Martin IngiIngvarsson, Ragnar FreyrPálsson, RunólfurThorgeirsson, GudmundurHalldórsson, Bjarni VilhjálmurHolm, HilmaKristjánsson, MárSulem, PatrickÞorsteinsdóttir, UnnurJónsdóttir, IngileifGudbjartsson, Daniel FStefansson, Kari2025-11-172025-11-172022-09-06Olafsdottir, T A, Bjarnadottir, K, Norddahl, G L, Halldórsson, G H, Melsted, P, Gunnarsdottir, K, Ivarsdottir, E, Olafsdottir, T, Arnthorsson, A O, Theódórs, F, Eyþórsson, E S, Helgason, D, Eggertsson, H P, Masson, G, Bjarnadottir, S, Sævarsdóttir, S, Runólfsdóttir, H L, Ólafsson, Í, Saemundsdottir, J, Sigurðsson, M I, Ingvarsson, R F, Pálsson, R, Thorgeirsson, G, Halldórsson, B V, Holm, H, Kristjánsson, M, Sulem, P, Þorsteinsdóttir, U, Jónsdóttir, I, Gudbjartsson, D F & Stefansson, K 2022, 'HLA alleles, disease severity, and age associate with T-cell responses following infection with SARS-CoV-2', Communications Biology, vol. 5, no. 1, 914, pp. 914. https://doi.org/10.1038/s42003-022-03893-w2399-3642593540258524246c-4139-469c-bfe2-8738490acbf536068292PubMedCentral: PMC944663085137309107unpaywall: 10.1038/s42003-022-03893-w000851290400007https://hdl.handle.net/20.500.11815/6001Funding Information: We thank all of the participants that contributed samples for this study for their invaluable contribution to the research. We also thank our research staff at the Patient Recruitment Center for their thorough work. Publisher Copyright: © 2022, The Author(s).Memory T-cell responses following SARS-CoV-2 infection have been extensively investigated but many studies have been small with a limited range of disease severity. Here we analyze SARS-CoV-2 reactive T-cell responses in 768 convalescent SARS-CoV-2-infected (cases) and 500 uninfected (controls) Icelanders. The T-cell responses are stable three to eight months after SARS-CoV-2 infection, irrespective of disease severity and even those with the mildest symptoms induce broad and persistent T-cell responses. Robust CD4+ T-cell responses are detected against all measured proteins (M, N, S and S1) while the N protein induces strongest CD8+ T-cell responses. CD4+ T-cell responses correlate with disease severity, humoral responses and age, whereas CD8+ T-cell responses correlate with age and functional antibodies. Further, CD8+ T-cell responses associate with several class I HLA alleles. Our results, provide new insight into HLA restriction of CD8+ T-cell immunity and other factors contributing to heterogeneity of T-cell responses following SARS-CoV-2 infection.4256484914eninfo:eu-repo/semantics/openAccessAllelesCD8-Positive T-LymphocytesCOVID-19/geneticsHumansSARS-CoV-2Severity of Illness IndexGeneral Agricultural and Biological SciencesGeneral Biochemistry,Genetics and Molecular BiologyMedicine (miscellaneous)SDG 3 - Good Health and Well-being/dk/atira/pure/researchoutput/researchoutputtypes/contributiontojournal/article10.1038/s42003-022-03893-w