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Newborn and child-like molecular signatures in older adults stem from TCR shifts across human lifespan.

ABSTRACT: 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-M1_58-66 (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.

SUBMITTER: van de Sandt CE

PROVIDER: S-EPMC10602853 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Newborn and child-like molecular signatures in older adults stem from TCR shifts across human lifespan.

van de Sandt Carolien E CE Nguyen Thi H O THO Gherardin Nicholas A NA Crawford Jeremy Chase JC Samir Jerome J Minervina Anastasia A AA Pogorelyy Mikhail V MV Rizzetto Simone S Szeto Christopher C Kaur Jasveen J Ranson Nicole N Sonda Sabrina S Harper Alice A Redmond Samuel J SJ McQuilten Hayley A HA Menon Tejas T Sant Sneha S Jia Xiaoxiao X Pedrina Kate K Karapanagiotidis Theo T Cain Natalie N Nicholson Suellen S Chen Zhenjun Z Lim Ratana R Clemens E Bridie EB Eltahla Auda A La Gruta Nicole L NL Crowe Jane J Lappas Martha M Rossjohn Jamie J Godfrey Dale I DI Thomas Paul G PG Gras Stephanie S Flanagan Katie L KL Luciani Fabio F Kedzierska Katherine K

Nature immunology 20230925 11

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 old ...[more]

PMID: 37749325

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Dataset Information

Newborn and child-like molecular signatures in older adults stem from TCR shifts across human lifespan.

Publications

Newborn and child-like molecular signatures in older adults stem from TCR shifts across human lifespan.

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