What question did this study set out to answer?

To investigate how the human disease-linked ZAP70 R360P mutation disrupts autoinhibition and drives autoimmune pathology through altered T cell receptor signaling.

February 2, 2021Science SignalingOpen Access

A disease-associated mutation that weakens ZAP70 autoinhibition enhances responses to weak and self-ligands

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Authors

LSLin ShenHunan Provincial Center for Disease Control and Prevention MMMehrdad MatloubianUniversity of California, San Francisco TKTheresa A. KadlecekUniversity of California, San Francisco

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Implication

Murine study reveals that mutated ZAP70 enhances T cell responses to self-antigens in mice, indicating a mechanism for broken immune tolerance.

Key Points

To investigate how the human disease-linked ZAP70 R360P mutation disrupts autoinhibition and drives autoimmune pathology through altered T cell receptor signaling.
Engineered mice harboring the ZAP70 R360P mutation with polyclonal TCR repertoires to evaluate T cell development and signaling.
Assessed follicular helper T cell expansion in R360P mice following lymphocytic choriomeningitis virus infection.
Introduced the OT-I transgenic TCR into mutant mice to test T cell reactivity against weak agonists and self-peptides.
Mice bearing the ZAP70 R360P mutation maintained normal T cell development while exhibiting increased baseline TCR signaling.
Infection with LCMV triggered elevated expansion of follicular helper T cells in R360P mice.
OT-I transgenic R360P T cells demonstrated heightened sensitivity and responsiveness to both weak peptide agonists and self-ligands.

Cite This Study

Shen et al. (2021) studied this question.

synapsesocial.com/papers/6a845b644e8c7cff228d75fd https://doi.org/10.1126/scisignal.abc4479

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Implication

Murine study reveals that mutated ZAP70 enhances T cell responses to self-antigens in mice, indicating a mechanism for broken immune tolerance.

A disease-associated mutation that weakens ZAP70 autoinhibition enhances responses to weak and self-ligands

Discussion

Member takes

Implication

Key Points

Cite This Study

A disease-associated mutation that weakens ZAP70 autoinhibition enhances responses to weak and self-ligands

Discussion

Member takes

Implication

Key Points

Cite This Study

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