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

Lore Billiet; Laurenz De Cock; Guillem Sanchez Sanchez; Rupert L Mayer; Glenn Goetgeluk; Stijn De Munter; Melissa Pille; Joline Ingels; Hanne Jansen; Karin Weening; Eva Pascal; Killian Raes; Sarah Bonte; Tessa Kerre; Niels Vandamme; Ruth Seurinck; Jana Roels; Marieke Lavaert; Filip Van Nieuwerburgh; Georges Leclercq; Tom Taghon; Francis Impens; Björn Menten; David Vermijlen; Bart Vandekerckhove

doi:10.1084/jem.20220942

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

J Exp Med. 2023 Jun 5;220(6):e20220942. doi: 10.1084/jem.20220942. Epub 2023 Mar 20.

Authors

Lore Billiet^#¹, Laurenz De Cock^#^{2

3}, Guillem Sanchez Sanchez^{4

5

6

7}, Rupert L Mayer^{2

8

9}, Glenn Goetgeluk^{1

3}, Stijn De Munter^{1

3}, Melissa Pille¹, Joline Ingels^{1

3}, Hanne Jansen¹, Karin Weening¹, Eva Pascal^{1

3}, Killian Raes¹, Sarah Bonte^{3

10

11}, Tessa Kerre^{1

3

10}, Niels Vandamme^{12

11}, Ruth Seurinck¹¹, Jana Roels^{12

11}, Marieke Lavaert¹, Filip Van Nieuwerburgh^{3

13}, Georges Leclercq^{1

3}, Tom Taghon^{1

3}, Francis Impens^{2

8

9}, Björn Menten², David Vermijlen^{4

5

6

7}, Bart Vandekerckhove^{1

3}

Affiliations

¹ Department of Diagnostic Sciences, Ghent University , Ghent, Belgium.
² Department of Biomolecular Medicine, Ghent University , Ghent, Belgium.
³ Cancer Research Institute Ghent , Ghent, Belgium.
⁴ Department of Pharmacotherapy and Pharmaceutics, Université Libre de Bruxelles , Brussels, Belgium.
⁵ Institute for Medical Immunology, Université Libre de Bruxelles , Brussels, Belgium.
⁶ Université Libre de Bruxelles Center for Research in Immunology, Université Libre de Bruxelles , Brussels, Belgium.
⁷ WELBIO Department, WEL Research Institute, Wavre, Belgium.
⁸ VIB-UGent Center for Medical Biotechnology, VIB , Ghent, Belgium.
⁹ VIB Proteomics Core, VIB , Ghent, Belgium.
¹⁰ Department of Internal Medicine and Pediatrics, Ghent University , Ghent, Belgium.
¹¹ Data Mining and Modeling for Biomedicine, VIB-UGent Center for Inflammation Research , Ghent, Belgium.
¹² VIB Single Cell Core, VIB , Ghent, Belgium.
¹³ Department of Pharmaceutics, Ghent University , Ghent, Belgium.

^# Contributed equally.

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Cell Differentiation
Cell Lineage
Humans
Receptors, Antigen, T-Cell, alpha-beta* / genetics
Receptors, Antigen, T-Cell, alpha-beta* / metabolism
T-Lymphocytes* / metabolism
Thymus Gland

Substances

Receptors, Antigen, T-Cell, alpha-beta