RT Journal Article
T1 Patients with CD3G mutations reveal a role for human CD3g in Treg diversity and suppressive function
A1 Rowe, Jared H
A1 Delmonte, Ottavia M
A1 Keles, Sevgi
A1 Stadinski, Brian D
A1 Dobbs, Adam K
A1 Henderson, Lauren A
A1 Yamazaki, Yasuhiro
A1 Allende Martínez, Luis Miguel
A1 Bonilla, Francisco A
A1 González Granado, Luis Ignacio
A1 Celikbilek Celik, Seyma
A1 Guner, Sukru N
A1 Kapakli, Hasan
A1 Yee, Christina
A1 Pai, Sung-Yun
A1 Huseby, Eric S
A1 Reisli, Ismail
A1 Regueiro González-Barros, José Ramón
A1 Notarangelo, Luigi D
AB Integrity of the T-cell receptor/CD3 complex is crucial for positive and negative selection of T cells in the thymus and for effector and regulatory functions of peripheral T lymphocytes. In humans, CD3D, CD3E, and CD3Z gene defects are a cause of severe immune deficiency and present early in life with increased susceptibility to infections. By contrast, CD3G mutations lead to milder phenotypes, mainly characterized by autoimmunity. However, the role of CD3g in establishing and maintaining immune tolerance has not been elucidated. In this manuscript, we aimed to investigate abnormalities of T-cell repertoire and function in patients with genetic defects in CD3G associated with autoimmunity. High throughput sequencing was used to study composition and diversity of the T-cell receptor b (TRB) repertoire in regulatory T cells (Tregs), conventional CD41 (Tconv), and CD81 T cells from 6 patientswith CD3Gmutations and healthy controls. Treg function was assessed by studying its ability to suppress proliferation of Tconv cells. Treg cells of patients with CD3G defects had reduced diversity, increased clonality, and reduced suppressive function. The TRB repertoire of Tconv cells from patients with CD3G deficiency was enriched for hydrophobic amino acids at positions 6 and 7 of the CDR3, a biomarker of self-reactivity. These data demonstrate that the T-cell repertoire of patients with CD3G mutations is characterized by a molecular signature that may contribute to the increased rate of autoimmunity associated with this condition.
PB American Society of Hematology
SN 1528-0020; 0006-4971
YR 2018
FD 2018-05-24
LK https://hdl.handle.net/20.500.14352/12713
UL https://hdl.handle.net/20.500.14352/12713
LA eng
NO Division of Intramural Research
NO National Institute of Allergy and Infectious Diseases
NO National Institutes of Health
DS Docta Complutense
RD 10 abr 2025