Combined immunodeficiency caused by pathogenic variants in the ZAP70 C-terminal SH2 domain.

ABSTRACT:

Introduction

ZAP-70, a protein tyrosine kinase recruited to the T cell receptor (TCR), initiates a TCR signaling cascade upon antigen stimulation. Mutations in the ZAP70 gene cause a combined immunodeficiency characterized by low or absent CD8+ T cells and nonfunctional CD4+ T cells. Most deleterious missense ZAP70 mutations in patients are located in the kinase domain but the impact of mutations in the SH2 domains, regulating ZAP-70 recruitment to the TCR, are not well understood.

Methods

Genetic analyses were performed on four patients with CD8 lymphopenia and a high resolution melting screening for ZAP70 mutations was developed. The impact of SH2 domain mutations was evaluated by biochemical and functional analyses as well as by protein modeling.

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SUBMITTER: Mongellaz C 

PROVIDER: S-EPMC10258307 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature