Materna, MarieCárdenas Mastrascusa, Paula PatriciaRegueiro González-Barros, José RamónBéziat, Vivien2024-08-072024-08-072024-03-22Marie Materna et al. ,The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants.Science383,eadh4059(2024).DOI:10.1126/science.adh40590036-807510.1126/science.adh4059https://hdl.handle.net/20.500.14352/107408We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre-TCRα expression. Low circulating naïve αβ T cell counts at birth persisted over time, with normal memory αβ and high γδ T cell counts. Their TCRα repertoire was biased, suggesting 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 naïve 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 than in the general population.engAttribution 4.0 Internationalhttp://creativecommons.org/licenses/by/4.0/journal articlehttps://doi.org/10.1126/science.adh4059https://www.science.org/doi/10.1126/science.adh4059open access612.017Inmunología2412 Inmunología