Read more about the Fellowship: www.cslfellowships.com.au/fellows-archive/dr-carolien-van-de-sandt-biography

And thanks to our funders:
@nhmrc.bsky.social, The Australian Research Council, the NIH, the Clifford Craig Foundation, Marie Skłodowska-Curie Actions, The University of Melbourne

Thanks everybody who contributed:
Hayley McQuilten, Jerome Samir, Oanh Nguyen, Ratana Lim, Jasveen Kaur, Simone Rizzetto, Auda Eltahla, Paul Thomas, Martha Lappas, Jamie Rossjohn, Stephanie Gras, Jane Crowe, Katie Flanagan, Fabio Luciani , Peter Doherty, @katherinekedz.bsky.social

Tejas also wrote a great lay version which can be found at the @thedohertyinst.bsky.social website: www.doherty.edu.au/news-events/...

#Openaccess

This study was supported by
#nhmrc, #arc_gov_au, #MSCActions, #EU_H2020

This study was a multi-institute collaboration between @thedohertyinst.bsky.social, @UniMelb, @whofluccmelb.bsky.social , @latrobeuni.bsky.social , @monashuniversity.bsky.social

We would like to thank all our collaborators on this work @HayleyMcQuilten, @MaletAban, @OanhNguyen, @SophieValkenburg @EmmaGrant, @SnehaSant, @JamieRossjohn, @graslab.bsky.social , @JaneCrowe

Conclusion: Public A2/M158-specific TCR clonotypes are long-lived. We identified a window of opportunity between 30-40 years of age, when optimal public TCRs and/or public-associated clonotypes could be boosted through novel vaccinations, so they can be maintained to older age.

We demonstrated that the lower probability of generation of older TCRb chains underpins the decrease in TCR similarity within the A2M1-specific TCRab repertoire of older adults over time.

Decline in adults public TCRs is compensated by expansion of similar TCRs which express public CDR3 motifs with strong avidity for A2M1. Older TCR repertoires lack public-CDR3 motifs, resulting in expansion of low similar TCRs with private CDR3 motifs & lower avidity for A2M1.

Young public clonotypes (associated with higher functionality) and older private clonotypes (associated with lower functionality) are long-lived and can be detected over the course of 12 years but gradually decline over time.

Adult TCR repertoires were relative stable across timepoints, the limited diversity resulted from broader TCRa gene usage. Heterogenic changes were observed in older TCR repertoires across timepoints, both the TCRa & TCRb chain contribute to diversifying older TCR repertoires.

We defined influenza-specific CD8 T cell immunity over 12 years directly ex vivo in cohort of adults & older adults. T cells were directed at the prominent/conserved HLA-A*02:01-restricted M1(58–66) peptide derived from influenza A viruses (A2M1)