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

ABSTRACT: We report humans with biallelic loss-of-function PTCRA rare variants impairing pre-TCR-⍺ expression. Low naive ⍺β T cell blood counts at birth persist over time with normal memory ⍺β and high γδ T cell counts. Early productive TCR-δ or TCR-⍺ rearrangements can rescue ⍺β T cell differentiation by stabilizing low levels of cell surface CD3. Only a minority of them are sick, with infection, lymphoproliferation, and/or autoimmunity. We also report that ~1/4,000 individuals from the Middle East and South Asia are homozygous for a hypomorphic PTCRA common variant. They have normal naive ⍺β T cell but high γδ T cell blood counts. Residual expression of their pre-TCR-⍺ enables differentiation of more ⍺β T cells. However, these patients have autoimmune conditions more commonly than the general population.

ORGANISM(S): Homo sapiens

PROVIDER: GSE243927 | GEO | 2024/02/14

REPOSITORIES: GEO

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