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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
Newborn and child-like molecular signatures in older adults stem from TCR shifts across human lifespan
Nature Immunology, Volume 24, No. 11, Year 2023
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Description
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. © 2023, The Author(s).
Authors & Co-Authors
Nguyen, Thi H.O.
Australia, Melbourne
University of Melbourne
Eltahla, Auda A.
Australia, Sydney
Unsw Sydney
Rossjohn, Jamie
Australia, Clayton
Monash University
United Kingdom, Cardiff
Cardiff University School of Medicine
Thomas, Paul G.
United States, Memphis
St. Jude Children's Research Hospital
Gras, Stéphanie Le
Australia, Melbourne
La Trobe University
Australia, Clayton
Monash University
Flanagan, Katie L.
Australia, Hobart
University of Tasmania
Australia, Melbourne
Rmit University
Australia, Launceston
Launceston General Hospital
Luciani, Fabio
Australia, Sydney
Unsw Sydney
Kedzierska, Katherine
Australia, Melbourne
University of Melbourne
Statistics
Citations: 1
Authors: 8
Affiliations: 11
Identifiers
Doi:
10.1038/s41590-023-01633-8
ISSN:
15292908
Research Areas
Genetics And Genomics
Maternal And Child Health