ArticleProceedings of the National Academy of Sciences of the United States of America2014
Effective functional maturation of invariant natural killer T cells is constrained by negative selection and T-cell antigen receptor affinity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- The RNA- and DNA-Binding Protein Y-Box Binding Protein 1 (YB-1) Regulates iNKT Cell Development.European journal of immunology · 2026Article
- Gluten-Free Diet Induces Small-Scale Changes Across Multiple T-Cell Subsets in NOD Mice.European journal of immunology · 2025Article
- Clonally expanded memory CD8Nature aging · 2023Article
- Destined for the intestine: thymic selection of TCRαβ CD8αα intestinal intraepithelial lymphocytes.Clinical and experimental immunology · 2023Review
- Markers and makers of NKT17 cells.Experimental & molecular medicine · 2023Review
- Modulation of TCR signalling components occurs prior to positive selection and lineage commitment in iNKT cells.Scientific reports · 2021Article
- SRSF1 plays a critical role in invariant natural killer T cell development and function.Cellular & molecular immunology · 2021Article
- Zeb1 represses TCR signaling, promotes the proliferation of T cell progenitors and is essential for NK1.1Cellular & molecular immunology · 2021Article
- Distinct organization of adaptive immunity in the long-lived rodent Spalax galili.Nature aging · 2021Article
- Invariant natural killer T cells balance B cell immunity.Immunological reviews · 2021Review
- Thymic development of unconventional T cells: how NKT cells, MAIT cells and γδ T cells emerge.Nature reviews. Immunology · 2020Review
- Quantitative Difference in PLZF Protein Expression Determines iNKT Lineage Fate and Controls Innate CD8 T Cell Generation.Cell reports · 2019Article
- The Protein Phosphatase Shp1 Regulates Invariant NKT Cell Effector Differentiation Independently of TCR and Slam Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- SLAM receptors foster iNKT cell development by reducing TCR signal strength after positive selection.Nature immunology · 2019Article
- The ins and outs of type I iNKT cell development.Molecular immunology · 2019Review
- Differential Activation of Hepatic Invariant NKT Cell Subsets Plays a Key Role in Progression of Nonalcoholic Steatohepatitis.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
- Endogenous lipid antigens for invariant natural killer T cells hold the reins in adipose tissue homeostasis.Immunology · 2018Review
- Key Residues at Third CDR3β Position Impact Structure and Antigen Recognition of Human Invariant NK TCRs.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- Development of invariant natural killer T cells.Current opinion in immunology · 2016Review
- CDR3β sequence motifs regulate autoreactivity of human invariant NKT cell receptors.Journal of autoimmunity · 2016Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
The self-reactivity of their T-cell antigen receptor (TCR) is thought to contribute to the development of immune regulatory cells, such as invariant NK T cells (iNKT). In the mouse, iNKT cells express TCRs composed of a unique Vα14-Jα18 rearrangement and recognize lipid antigens presented by CD1d molecules. We created mice expressing a transgenic TCR-β chain that confers high affinity for self-lipid/CD1d complexes when randomly paired with the mouse iNKT Vα14-Jα18 rearrangement to study their development. We show that although iNKT cells undergo agonist selection, their development is also shaped by negative selection in vivo. In addition, iNKT cells that avoid negative selection in these mice express natural sequence variants of the canonical TCR-α and decreased affinity for self/CD1d. However, limiting the affinity of the iNKT TCRs for "self" leads to inefficient Egr2 induction, poor expression of the iNKT lineage-specific zinc-finger transcription factor PLZF, inadequate proliferation of iNKT cell precursors, defects in trafficking, and impaired effector functions. Thus, proper development of fully functional iNKT cells is constrained by a limited range of TCR affinity that plays a key role in triggering the iNKT cell-differentiation pathway. These results provide a direct link between the affinity of the TCR expressed by T-cell precursors for self-antigens and the proper development of a unique population of lymphocytes essential to immune responses.
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