ArticleJournal of immunology (Baltimore, Md. : 1950)2014
The ability to rearrange dual TCRs enhances positive selection, leading to increased Allo- and Autoreactive T cell repertoires.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 33 citations in OpenAlex.
- Non-canonical clonal expansion of autoreactive CD8Cell insight · 2026Article
- The TCR in CAR T cell therapy: use it or lose it?Cancer gene therapy · 2026Review
- Dual T cell receptor expression provides intrinsic advantage for agonist selection of thymic FoxP3+ regulatory T cells (Tregs) in the neonatal thymus.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Unraveling CD8American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Review
- Antigen-driven T cell responses in rheumatic diseases: insights from T cell receptor repertoire studies.Nature reviews. Rheumatology · 2025Review
- Immune and non-immune mediators in the fibrosis pathogenesis of salivary gland in Sjögren's syndrome.Frontiers in immunology · 2024Review
- When inflammatory stressors dramatically change, disease phenotypes may transform between autoimmune hematopoietic failure and myeloid neoplasms.Frontiers in immunology · 2024Review
- The screening, identification, design and clinical application of tumor-specific neoantigens for TCR-T cells.Molecular cancer · 2023Review
- Dual TCR-Expressing T Cells in Cancer: How Single-Cell Technologies Enable New Investigation.ImmunoHorizons · 2023Article
- Dual receptor T cells mediate effective antitumor immune responses via increased recognition of tumor antigens.Journal for immunotherapy of cancer · 2023Article
- Analysis of T-Cell Receptor Repertoire in Transplantation: Fingerprint of T Cell-mediated Alloresponse.Frontiers in immunology · 2021Review
- TCRα reporter mice reveal contribution of dual TCRα expression to T cell repertoire and function.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Learning the next-generation sequencing alphabet of immune reconstitution: factors determining CD8Haematologica · 2019Article
- Dual TCR T Cells: Identity Crisis or Multitaskers?Journal of immunology (Baltimore, Md. : 1950) · 2019Review
- Bystander T Cells: A Balancing Act of Friends and Foes.Trends in immunology · 2018Review
- Proinflammatory Dual Receptor T Cells in Chronic Graft-versus-Host Disease.Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation · 2017Article
- Article
- Cutting Edge: Dual TCRα Expression Poses an Autoimmune Hazard by Limiting Regulatory T Cell Generation.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Article
- Low-Affinity Memory CD8+ T Cells Mediate Robust Heterologous Immunity.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Thymic selection is designed to ensure TCR reactivity to foreign Ags presented by self-MHC while minimizing reactivity to self-Ags. We hypothesized that the repertoire of T cells with unwanted specificities such as alloreactivity or autoreactivity are a consequence of simultaneous rearrangement of both TCRα loci. We hypothesized that this process helps maximize production of thymocytes capable of successfully completing thymic selection, but results in secondary TCRs that escape stringent selection. In T cells expressing two TCRs, one TCR can mediate positive selection and mask secondary TCR from negative selection. Examination of mice heterozygous for TRAC (TCRα(+/-)), capable of only one functional TCRα rearrangement, demonstrated a defect in generating mature T cells attributable to decreased positive selection. Elimination of secondary TCRs did not broadly alter the peripheral T cell compartment, though deep sequencing of TCRα repertoires of dual TCR T cells and TCRα(+/-) T cells demonstrated unique TCRs in the presence of secondary rearrangements. The functional impact of secondary TCRs on the naive peripheral repertoire was evidenced by reduced frequencies of T cells responding to autoantigen and alloantigen peptide-MHC tetramers in TCRα(+/-) mice. T cell populations with secondary TCRs had significantly increased ability to respond to altered peptide ligands related to their allogeneic ligand as compared with TCRα(+/-) cells, suggesting increased breadth in peptide recognition may be a mechanism for their reactivity. Our results imply that the role of secondary TCRs in forming the T cell repertoire is perhaps more significant than what has been assumed.
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Registered trials
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