ArticleImmunity2007
Opposing functions of the T cell receptor kinase ZAP-70 in immunity and tolerance differentially titrate in response to nucleotide substitutions.
Article in Immunity, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
82 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- Genome-wide association analyses of autoimmune hypothyroidism reveal autoimmune and thyroid-specific contributions and an inverse relationship with cancer risk.Nature genetics · 2026Pooled it
- Pathological IgE Production in Inborn Errors of Immunity and Beyond.Immunological reviews · 2025Review
- A partial human LCK defect causes a T cell immunodeficiency with intestinal inflammation.The Journal of experimental medicine · 2024Article
- Molecular consideration relevant to the mechanism of the comorbidity between psoriasis and systemic lupus erythematosus (Review).Experimental and therapeutic medicine · 2023Review
- Construction of a T cell receptor signaling range for spontaneous development of autoimmune disease.The Journal of experimental medicine · 2023Article
- Covalent TCR-peptide-MHC interactions induce T cell activation and redirect T cell fate in the thymus.Nature communications · 2022Article
- ZAP70, too little, too much can lead to autoimmunity.Immunological reviews · 2022Review
- Genome editing to define the function of risk loci and variants in rheumatic disease.Nature reviews. Rheumatology · 2021Review
- A disease-associated mutation that weakens ZAP70 autoinhibition enhances responses to weak and self-ligands.Science signaling · 2021Article
- Novel ZAP-70-Related Immunodeficiency Presenting with Epstein-Barr Virus Lymphoproliferative Disorder and Hemophagocytic Lymphohistiocytosis.Case reports in immunology · 2021Article
- 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
- miR-181a/b-1 controls thymic selection of Treg cells and tunes their suppressive capacity.PLoS biology · 2019Article
- An association study in PTPN22 suggests that is a risk factor to Takayasu's arteritis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2019Article
- Malt1 self-cleavage is critical for regulatory T cell homeostasis and anti-tumor immunity in mice.European journal of immunology · 2018Article
- ZAP-70 in Signaling, Biology, and Disease.Annual review of immunology · 2018Review
- The Balance of Th17 versus Treg Cells in Autoimmunity.International journal of molecular sciences · 2018Review
- TCR Signaling Abnormalities in Human Th2-Associated Atopic Disease.Frontiers in immunology · 2018Review
- Mice Deficient in Nucleoporin Nup210 Develop Peripheral T Cell Alterations.Frontiers in immunology · 2018Article
- B cell autoimmunity at the extremes.Nature immunology · 2017Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Null mutations that cripple T cell receptor (TCR) signaling explain rare primary immunodeficiencies, but it is not understood why more common polymorphisms that lead to subtle TCR signaling defects are paradoxically associated with autoimmunity. Here we analyzed how a series of Zap70 variants with step-wise decreases in TCR signaling impacted upon opposing TCR functions of immunity and tolerance. One Zap70 variant, murdock, moderately decreased TCR signaling and thymic selection without compromising immunological tolerance, whereas a more severe Zap70 defect, mrtless, abolished thymic-positive selection and led to immunodeficiency. Signaling capacities between these two thresholds disproportionately compromised negative selection and Foxp3(+) regulatory T cell formation, creating a cellular imbalance between immunogenic and tolerogenic functions that resulted in the excessive production of autoantibodies and immunoglobulin E (IgE). The pleiotropic functions of ZAP-70 and their differential response to graded variation provide a paradigm for understanding the complex outcomes of human genetic variation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.