ArticleThe Journal of experimental medicine2009
A hypomorphic allele of ZAP-70 reveals a distinct thymic threshold for autoimmune disease versus autoimmune reactivity.
Article in The Journal of experimental medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
What it found
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Who cites it
48 citing papers in PubMed.
- Endogenous antigens shape the transcriptome and TCR repertoire in an autoimmune arthritis model.The Journal of clinical investigation · 2024Article
- STING-STAT6 Signaling Pathway Promotes IL-4Immune network · 2024Article
- Kidins220 and Aiolos promote thymic iNKT cell development by reducing TCR signals.Science advances · 2024Article
- A partial human LCK defect causes a T cell immunodeficiency with intestinal inflammation.The Journal of experimental medicine · 2024Article
- A Story of Kinases and Adaptors: The Role of Lck, ZAP-70 and LAT in Switch Panel Governing T-Cell Development and Activation.Biology · 2023Review
- Construction of a T cell receptor signaling range for spontaneous development of autoimmune disease.The Journal of experimental medicine · 2023Article
- Regulatory T cell homeostasis: Requisite signals and implications for clinical development of biologics.Clinical immunology (Orlando, Fla.) · 2023Review
- The RAG1 Ubiquitin Ligase Domain Stimulates Recombination of TCRβ and TCRα Genes and Influences Development of αβ T Cell Lineages.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- ZAP70, too little, too much can lead to autoimmunity.Immunological reviews · 2022Review
- Negative Regulation of Zap70 by Lck Forms the Mechanistic Basis of Differential Expression in CD4 and CD8 T Cells.Frontiers in immunology · 2022Article
- Cbl-b deficiency prevents functional but not phenotypic T cell anergy.The Journal of experimental medicine · 2021Article
- A disease-associated mutation that weakens ZAP70 autoinhibition enhances responses to weak and self-ligands.Science signaling · 2021Article
- A novel zeta-associated protein 70 homozygous mutation causing combined immunodeficiency presenting as neonatal autoimmune hemolytic anemia.Immunologic research · 2021Article
- Thymus and autoimmunity.Seminars in immunopathology · 2021Review
- Naturally Occurring Genetic Alterations in Proximal TCR Signaling and Implications for Cancer Immunotherapy.Frontiers in immunology · 2021Review
- Reporters of TCR signaling identify arthritogenic T cells in murine and human autoimmune arthritis.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- T Cell Receptor Expression Timing and Signal Strength in the Functional Differentiation of Invariant Natural Killer T Cells.Frontiers in immunology · 2019Review
- TCR signal strength controls thymic differentiation of iNKT cell subsets.Nature communications · 2018Article
- Thymic tolerance as a key brake on autoimmunity.Nature immunology · 2018Review
- ZAP-70 in Signaling, Biology, and Disease.Annual review of immunology · 2018Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
ZAP-70 is critical for T cell receptor (TCR) signaling. Tyrosine to phenylalanine mutations of Y315 and Y319 in ZAP-70 suggest these residues function to recruit downstream effector molecules, but mutagenesis and crystallization studies reveal that these residues also play an important role in autoinhibition ZAP-70. To address the importance of the scaffolding function, we generated a zap70 mutant mouse (YYAA mouse) with Y315 and Y319 both mutated to alanines. These YYAA mice reveal that the scaffolding function is important for normal development and function. Moreover, the YYAA mice have many similarities to a previously identified ZAP-70 mutant mouse, SKG, which harbors a distinct hypomorphic mutation. Both YYAA and SKG mice have impaired T cell development and hyporesponsiveness to TCR stimulation, markedly reduced numbers of thymic T regulatory cells and defective positive and negative selection. YYAA mice, like SKG mice, develop rheumatoid factor antibodies, but fail to develop autoimmune arthritis. Signaling differences that result from ZAP-70 mutations appear to skew the TCR repertoire in ways that differentially influence propensity to autoimmunity versus autoimmune disease susceptibility. By uncoupling the relative contribution from T regulatory cells and TCR repertoire during thymic selection, our data help to identify events that may be important, but alone are insufficient, for the development of autoimmune disease.
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Registered trials
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