The immunopathological landscape of human pre-TCRα deficiency: from rare to common variants
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1020588 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR26158300_1.fastq.gz | Fastqsanger.gz | |||
| SRR26158300_2.fastq.gz | Fastqsanger.gz | |||
| SRR26158301_1.fastq.gz | Fastqsanger.gz | |||
| SRR26158301_2.fastq.gz | Fastqsanger.gz | |||
| SRR26158302_1.fastq.gz | Fastqsanger.gz |
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Project description:We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre-α T cell receptor (pre-TCRα) expression. Low circulating naive αβ T cell counts at birth persisted over time, with normal memory αβ and high γδ T cell counts. Their TCRα repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue αβ 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 αβ T cell counts but high γδ T cell counts. Although residual pre-TCRα expression drove the differentiation of more αβ T cells, autoimmune conditions were more frequent in these patients compared with the general population.
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