journal contribution
posted on 2024-02-26, 23:56 authored by Carolien E van de Sandt, Thi HO Nguyen, Nicholas A Gherardin, Jeremy Chase Crawford, Jerome Samir, Anastasia A Minervina, Mikhail V Pogorelyy, Simone Rizzetto, Christopher SzetoChristopher Szeto, Jasveen Kaur, Nicole Ranson, Sabrina Sonda, Alice Harper, Samuel J Redmond, Hayley A McQuilten, Tejas Menon, Sneha Sant, Xiaoxiao Jia, Kate Pedrina, Theo Karapanagiotidis, Natalie Cain, Suellen Nicholson, Zhenjun Chen, Ratana Lim, E Bridie Clemens, Auda Eltahla, Nicole L La Gruta, Jane Crowe, Martha Lappas, Jamie Rossjohn, Dale I Godfrey, Paul G Thomas, Stephanie GrasStephanie Gras, Katie L Flanagan, Fabio Luciani, Katherine Kedzierska CD8+ T cells provide robust antiviral immunity, but how epitope-specific T cells evolve across the human lifespan is unclear. Here we defined CD8+ T cell immunity directed at the prominent influenza epitope HLA-A*02:01-M158–66 (A2/M158) across four age groups at phenotypic, transcriptomic, clonal and functional levels. We identify a linear differentiation trajectory from newborns to children then adults, followed by divergence and a clonal reset in older adults. Gene profiles in older adults closely resemble those of newborns and children, despite being clonally distinct. Only child-derived and adult-derived A2/M158+CD8+ T cells had the potential to differentiate into highly cytotoxic epitope-specific CD8+ T cells, which was linked to highly functional public T cell receptor (TCR)αβ signatures. Suboptimal TCRαβ signatures in older adults led to less proliferation, polyfunctionality, avidity and recognition of peptide mutants, although displayed no signs of exhaustion. These data suggest that priming T cells at different stages of life might greatly affect CD8+ T cell responses toward viral infections.
Funding
This work was supported by the ARC-Discovery grant to K.K., F.L. and S.G. (DP190102704), the Clifford Craig Foundation Project Grant to K.F. and K.K. (186), the Research Grants Council of the Hong Kong Special Administrative Region, China (T11-712/19-N) to K.K. and the NHMRC Leadership Investigator Grant to K.K. (1173871). C.E.S. received funding from the European Union's Horizon 2020 research program under the Marie Sklodowska-Curie Grant agreement (792532) and is supported by the ARC-DECRA Fellowship (DE200100185) and the UoM Establishment Grant. F.L. was supported by the National Health and Medical Research Council, Australia (project grant 1121643) and Career Development Fellow (1128416). T.H.O.N. is supported by the NHMRC Emerging Leadership Level 1 Investigator Grant (1194036), N.A.G. is supported by the ARC-DECRA Fellowship (DE210100705), E.B.C. is supported by a NHMRC Peter Doherty Fellowship (1091516), J.R. and N.L.L.G. are supported by NHMRC Leadership Investigator grants, S.G. is supported by NHMRC Senior Research Fellowship (1159272), D.I.G. was supported by an NHMRC Senior Principal Research Fellowship (1117766) and subsequently by an NHMRC investigator grant (2008913). J.C.C., A.A.M., M.V.P. and P.G.T. are supported by NIH NIAID R01 AI136514, U01AI150747 and ALSAC at St. Jude.
History
Publication Date
2023-11-01Journal
Nature ImmunologyVolume
24Pagination
1890-1907Publisher
Springer NatureISSN
1529-2908Rights Statement
© The Author(s) 2023
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