The immunopathological landscape of human pre-TCRα deficiency: from rare to common variants

We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre–a T cell receptor (pre-TCRa) expression. Low circulating naive ab T cell counts at birth persisted over time, with normal memory ab and high gd T cell counts. Their TCRa repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue ab T cell development. Only a minority of these individuals were sick, with infection, lymphoproliferation, and/or autoimmunity. We also report that 1 in 4000 individuals from the Middle East and South Asia are homozygous for a common hypomorphic PTCRA variant. They had normal circulating naive ab T cell counts but high gd T cell counts. Although residual pre-TCRa expression drove the differentiation of more ab T cells, autoimmune conditions were more frequent in these patients compared with the general population.
, , , # The immunopathological landscape of human pre-TCRa deficiency: From rare to common variants

Raw Data of *in vitro* study.

### Datasets included:

1\) Western Blot: Uncropped membranes of the paper's figures.

We assessed the expression of PTCRA variants by extracting total protein from HEK293T cells 48 hours after transfection with the various pCMV6 plasmids encoding the PTCRA variants. For each conditions, we separated 20 mg of total protein by SDS-PAGE and immunoblotting was performed with antibodies against the DDK Tag (1:3000, HRP-coupled, M2, no. A8592, Sigma-Aldrich), PTCRA (1:3000, PA5-95578, Invitrogen), glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (1:5000, FL335, no. sc47724 HRP, Santa Cruz Biotechnology) or vinculin (1:5000, EPR8185, no. ab129002, Abcam). Staining was detected with the Clarity Western ECL substrate (Biorad, no. 1705061) or SuperSignal West Femto (ThermoScientific, no. 34096) with ChemiDoc MP (Biorad).

2\) Rawdata of PTCRA qPCR.

HEK293T cells were t...