
SLAM-associated protein (SAP) regulates the developmental programming and TCR repertoire of innate-like gamma delta (γδ) T cell subsets, including γδT17, γδT1, and γδNKT cells, at multiple checkpoints during thymic development.


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During thymic development, most γδ T cells acquire innate-like characteristics that are critical for their function in tumor surveillance, infectious disease, and tissue repair. The mechanisms, however, that regulate γδ T cell developmental programming remain unclear. Recently, we demonstrated that the SLAM-SAP signaling pathway regulates the development and function of multiple innate-like γδ T cell subsets. Here, we used a single-cell proteogenomics approach to identify SAP-dependent developmental checkpoints and to define the SAP-dependent γδ TCR repertoire. SAP deficiency resulted in both a significant loss of an immature Gzma + Blk+Etv5+Tox2+ γδT17 precursor population, and a significant increase in Cd4+Cd8+ Rorc+Ptcra+Rag1+ thymic γδ T cells. SAP-dependent diversion of embryonic day 17 thymic γδ T cell clonotypes into the αβ T cell developmental pathway was associated with a decreased frequency of mature clonotypes in neonatal thymus, and an altered γδ TCR repertoire in the periphery. Finally, we identify TRGV4/TRAV13-4(DV7)-expressing T cells as a novel, SAP-dependent Vγ4 γδT1 subset. Together, the data suggest that SAP-dependent γδ/αβ T cell lineage commitment regulates γδ T cell developmental programming and shapes the γδ TCR repertoire. 

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### Competing Interest Statement

The authors have declared no competing interest.

 [1]: pending:yes

SLAM/SAP signaling regulates discrete γδ T cell developmental checkpoints and shapes the innate-like γδ TCR repertoire

mapping-the-developmental-trajectories-and-tcr-repertoire-of-sap-dependent-innate-like-gamma-delta-γδ-t-cells


Mapping the Developmental Trajectories and TCR Repertoire of SAP-Dependent Innate-Like Gamma Delta (γδ) T Cells
