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Ghent University Academic Bibliography2000-01-01T00:00+00:001monthlySingle-cell profiling identifies a novel human polyclonal unconventional T cell lineage
https://biblio.ugent.be/publication/01GYYXFX77KJ2AKMCZYSM8WVV3
Billiet, LoreDe Cock, LaurenzSanchez Sanchez, GuillemMayer, RupertGoetgeluk, GlennDe Munter, StijnPille, MelissaIngels, JolineJansen, HanneWeening, KarinPascal, EvaRaes, KillianBonte, SarahKerre, TessaVandamme, NielsSeurinck, RuthRoels, JanaLavaert, MariekeVan Nieuwerburgh, FilipLeclercq, GeorgesTaghon, TomImpens, FrancisMenten, BjörnVermijlen, DavidVandekerckhove, Bart2023Billiet et al. identify the post-thymic progeny of the agonist-selected CD10(+) PD-1(+) precursors in humans based on shared characteristics of the T cell receptor repertoire and the transcriptome. This lineage represents a well-defined but heterogeneous, unconventional TCR alpha beta(+) lineage mostly confined within the CD8(+) Helios(+) T cells.
In the human thymus, a CD10(+) PD-1(+) TCR alpha beta(+) differentiation pathway diverges from the conventional single positive T cell lineages at the early double-positive stage. Here, we identify the progeny of this unconventional lineage in antigen-inexperienced blood. These unconventional T cells (UTCs) in thymus and blood share a transcriptomic profile, characterized by hallmark transcription factors (i.e., ZNF683 and IKZF2), and a polyclonal TCR repertoire with autoreactive features, exhibiting a bias toward early TCR alpha chain rearrangements. Single-cell RNA sequencing confirms a common developmental trajectory between the thymic and blood UTCs and clearly delineates this unconventional lineage in blood. Besides MME+ recent thymic emigrants, effector-like clusters are identified in this heterogeneous lineage. Expression of Helios and KIR and a decreased CD8 beta expression are characteristics of this lineage. This UTC lineage could be identified in adult blood and intestinal tissues. In summary, our data provide a comprehensive characterization of the polyclonal unconventional lineage in antigen-inexperienced blood and identify the adult progeny.application/pdfhttps://biblio.ugent.be/publication/01GYYXFX77KJ2AKMCZYSM8WVV3http://hdl.handle.net/1854/LU-01GYYXFX77KJ2AKMCZYSM8WVV3http://doi.org/10.1084/jem.20220942https://biblio.ugent.be/publication/01GYYXFX77KJ2AKMCZYSM8WVV3/file/01GZXCYPK6N1ZCRW9ZAPZMXW41engRockefeller University PressCreative Commons Attribution-NonCommercial-ShareAlike 4.0 International Public License (CC BY-NC-SA 4.0)info:eu-repo/semantics/openAccessJOURNAL OF EXPERIMENTAL MEDICINEISSN: 0022-1007ISSN: 1540-9538Medicine and Health SciencesBiology and Life SciencesImmunologyImmunology and AllergySingle-cell profiling identifies a novel human polyclonal unconventional T cell lineagejournalArticleinfo:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion