Single-cell profiling identifies a novel human polyclonal unconventional T cell lineage

Author:

Billiet Lore1ORCID,De Cock Laurenz23ORCID,Sanchez Sanchez Guillem4567ORCID,Mayer Rupert L.289ORCID,Goetgeluk Glenn13ORCID,De Munter Stijn13ORCID,Pille Melissa1ORCID,Ingels Joline13ORCID,Jansen Hanne1ORCID,Weening Karin1ORCID,Pascal Eva13ORCID,Raes Killian1ORCID,Bonte Sarah31011ORCID,Kerre Tessa1310ORCID,Vandamme Niels1211ORCID,Seurinck Ruth11ORCID,Roels Jana1211ORCID,Lavaert Marieke1ORCID,Van Nieuwerburgh Filip313ORCID,Leclercq Georges13ORCID,Taghon Tom13ORCID,Impens Francis289ORCID,Menten Björn2ORCID,Vermijlen David4567ORCID,Vandekerckhove Bart13ORCID

Affiliation:

1. Department of Diagnostic Sciences, Ghent University 1 , Ghent, Belgium

2. Department of Biomolecular Medicine, Ghent University 2 , Ghent, Belgium

3. Cancer Research Institute Ghent 3 , Ghent, Belgium

4. Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles 4 , Brussels, Belgium

5. Institute for Medical Immunology, Université Libre de Bruxelles 5 , Brussels, Belgium

6. Université Libre de Bruxelles Center for Research in Immunology, Université Libre de Bruxelles 6 , Brussels, Belgium

7. 13WELBIO Department, WEL Research Institute, Wavre, Belgium

8. VIB-UGent Center for Medical Biotechnology, VIB 7 , Ghent, Belgium

9. VIB Proteomics Core, VIB 8 , Ghent, Belgium

10. Department of Internal Medicine and Pediatrics, Ghent University 9 , Ghent, Belgium

11. Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation Research 11 , Ghent, Belgium

12. VIB Single Cell Core, VIB 10 , Ghent, Belgium

13. Department of Pharmaceutics, Ghent University 12 , Ghent, Belgium

Abstract

In the human thymus, a CD10+ PD-1+ TCRαβ+ 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 TCRα 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 CD8β 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.

Funder

Research Foundation Flanders

Stichting Tegen Kanker

GOA

Fonds De La Recherche Scientifique

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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