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Publication : The immunopathological landscape of human pre-TCRα deficiency: From rare to common variants.

First Author  Materna M Year  2024
Journal  Science Volume  383
Issue  6686 Pages  eadh4059
PubMed ID  38422122 Mgi Jnum  J:346607
Mgi Id  MGI:7610938 Doi  10.1126/science.adh4059
Citation  Materna M, et al. (2024) The immunopathological landscape of human pre-TCRalpha deficiency: From rare to common variants. Science 383(6686):eadh4059
abstractText  We describe humans with rare biallelic loss-of-function PTCRA variants impairing pre-alpha T cell receptor (pre-TCRalpha) expression. Low circulating naive alphabeta T cell counts at birth persisted over time, with normal memory alphabeta and high gammadelta T cell counts. Their TCRalpha repertoire was biased, which suggests that noncanonical thymic differentiation pathways can rescue alphabeta 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 alphabeta T cell counts but high gammadelta T cell counts. Although residual pre-TCRalpha expression drove the differentiation of more alphabeta T cells, autoimmune conditions were more frequent in these patients compared with the general population.
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