
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.08.17.608295
preprint
1
Article
Tissue determinants of the human T cell receptor repertoire.
Sureshchandra Suhas http://orcid.org/0000-0002-4141-8564

Henderson James
Levendosky Elizabeth
Bhattacharyya Sankalan
Kastenschmidt Jenna M http://orcid.org/0000-0002-0067-5142

Sorn Andrew M http://orcid.org/0000-0001-8660-1533

Mitul Mahina Tabassum http://orcid.org/0000-0002-5344-6810

Benchorin Aviv
Batucal Kyle
Daugherty Allyssa http://orcid.org/0000-0001-8428-0422

Murphy Samuel JH
Thakur Chandrani http://orcid.org/0000-0003-2833-0610

Trask Douglas http://orcid.org/0000-0003-0550-442X

Ahuja Gurpreet http://orcid.org/0000-0002-3196-0819

Moisan Annie http://orcid.org/0000-0002-4944-4548

Tiffeau-Mayer Andreas http://orcid.org/0000-0002-6643-7622

Saligrama Naresha http://orcid.org/0000-0003-2526-7150

Wagar Lisa E http://orcid.org/0000-0001-5980-3586

19 8 2024
2024.08.17.608295https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.08.17.608295
nihpp-2024.08.17.608295.pdf
98% of T cells reside in tissues, yet nearly all human T cell analyses are performed from peripheral blood. We single-cell sequenced 5.7 million T cells from ten donors' autologous blood and tonsils and sought to answer key questions about T cell receptor biology previously unanswerable by smaller-scale experiments. We identified distinct clonal expansions and distributions in blood compared to tonsils, with surprisingly low (1-7%) clonal sharing. These few shared clones exhibited divergent phenotypes across bodily sites. Analysis of antigen-specific CD8 T cells revealed location as a main determinant of frequency, phenotype, and immunodominance. Finally, diversity estimates from the tissue recalibrates current repertoire diversity estimates, and we provide a refined estimate of whole-body repertoire. Given the tissue-restricted nature of T cell phenotypes, functions, differentiation, and clonality revealed by this dataset, we conclude that tissue analyses are crucial for accurate repertoire analysis and monitoring changes after perturbing therapies.
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pmc
