Dryad
Published February 27, 2024 | Version v1
Dataset Open

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

Authors/Creators

  • 1. Imagine Institute for Genetic Diseases
  • 2. National Institute of Allergy and Infectious Diseases
  • 3. National Institutes of Health
  • 4. Children's Hospital of Philadelphia
  • 5. Institut Cochin
  • 6. Pitié-Salpêtrière Hospital
  • 7. McGill University
  • 8. Uppsala University
  • 9. KU Leuven
  • 10. Centogene (Germany)
  • 11. Rockefeller University
  • 12. Sidra Medical and Research Center
  • 13. Helix (United States)
  • 14. Berlin Institute of Health
  • 15. Tabriz University of Medical Sciences
  • 16. University of Pennsylvania
  • 17. Uppsala University Hospital
  • 18. Inserm
  • 19. Necker-Enfants Malades Hospital
  • 20. Complutense University of Madrid
  • 21. King Faisal Specialist Hospital & Research Centre
  • 22. Dasman Diabetes Institute
  • 23. University of Antwerp
  • 24. Centre Hospitalier Universitaire Sainte-Justine
  • 25. Centro de Biología Molecular Severo Ochoa
  • 26. Isfahan University of Medical Sciences
  • 27. Ahvaz Jundishapur University of Medical Sciences
  • 28. Zanjan University of Medical Sciences
  • 29. Institute for Research in Fundamental Sciences
  • 30. Shiraz University of Medical Sciences
  • 31. Tehran University of Medical Sciences
  • 32. Tokyo Medical and Dental University
  • 33. Kumamoto Medical Center
  • 34. National Defense Medical College
  • 35. Aix-Marseille University
  • 36. Hamad bin Khalifa University

Description

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.

Files

README.md

Files (139.2 kB)

Name Size Download all
md5:dd676e51e810a7e5bcf07e70adc631c2
16.5 kB Download
md5:f0fc30f9550b1acd2b84062ca9aa1cbb
1.5 kB Preview Download
md5:70aabfd732898b1f8799b879cfbd1a73
121.3 kB Preview Download