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

Billiet 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.

Publication year:2023

Accessibility:Open