ArticlePLoS biology2010
Innate-like control of human iNKT cell autoreactivity via the hypervariable CDR3beta loop.
Article in PLoS biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 68 citations in OpenAlex.
- Relatively low level of antigen-specific monocytes detected in blood from untreated tuberculosis patients using CD4+ T-cell receptor tetramers.PLoS pathogens · 2012Trial
- Antigen-driven T cell responses in rheumatic diseases: insights from T cell receptor repertoire studies.Nature reviews. Rheumatology · 2025Review
- Intestinal mucosal immunity and type 1 diabetes: Non-negligible communication between gut and pancreas.Diabetes, obesity & metabolism · 2025Review
- Lipidomic scanning of self-lipids identifies headless antigens for natural killer T cells.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Thymic development of human natural killer T cells: recent advances and implications for immunotherapy.Frontiers in immunology · 2024Review
- Severity of critical illness correlates with CD3-low expression on iNKT-cells among septic surgical patients.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- CD8Immunity · 2023Article
- Towards a better understanding of human iNKT cell subpopulations for improved clinical outcomes.Frontiers in immunology · 2023Review
- Article
- Transnuclear mice reveal Peyer's patch iNKT cells that regulate B-cell class switching to IgG1.The EMBO journal · 2019Article
- Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting.Cancer cell · 2018Article
- The versatility of the CD1 lipid antigen presentation pathway.Immunology · 2018Review
- Lipids hide or step aside for CD1-autoreactive T cell receptors.Current opinion in immunology · 2018Review
- T cell autoreactivity directed toward CD1c itself rather than toward carried self lipids.Nature immunology · 2018Article
- Key Residues at Third CDR3β Position Impact Structure and Antigen Recognition of Human Invariant NK TCRs.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- CDR3β sequence motifs regulate autoreactivity of human invariant NKT cell receptors.Journal of autoimmunity · 2016Article
- Cholesteryl esters stabilize human CD1c conformations for recognition by self-reactive T cells.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Atypical natural killer T-cell receptor recognition of CD1d-lipid antigens.Nature communications · 2016Article
- Mouse and Human CD1d-Self-Lipid Complexes Are Recognized Differently by Murine Invariant Natural Killer T Cell Receptors.PloS one · 2016Article
- Structural and Functional Changes of the Invariant NKT Clonal Repertoire in Early Rheumatoid Arthritis.Journal of immunology (Baltimore, Md. : 1950) · 2015Article
Corrections and comments
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Authors and funding
10 authors at 5 institutions in 3 countries.
Funding
Abstract
Invariant Natural Killer T cells (iNKT) are a versatile lymphocyte subset with important roles in both host defense and immunological tolerance. They express a highly conserved TCR which mediates recognition of the non-polymorphic, lipid-binding molecule CD1d. The structure of human iNKT TCRs is unique in that only one of the six complementarity determining region (CDR) loops, CDR3beta, is hypervariable. The role of this loop for iNKT biology has been controversial, and it is unresolved whether it contributes to iNKT TCR:CD1d binding or antigen selectivity. On the one hand, the CDR3beta loop is dispensable for iNKT TCR binding to CD1d molecules presenting the xenobiotic alpha-galactosylceramide ligand KRN7000, which elicits a strong functional response from mouse and human iNKT cells. However, a role for CDR3beta in the recognition of CD1d molecules presenting less potent ligands, such as self-lipids, is suggested by the clonal distribution of iNKT autoreactivity. We demonstrate that the human iNKT repertoire comprises subsets of greatly differing TCR affinity to CD1d, and that these differences relate to their autoreactive functions. These functionally different iNKT subsets segregate in their ability to bind CD1d-tetramers loaded with the partial agonist alpha-linked glycolipid antigen OCH and structurally different endogenous beta-glycosylceramides. Using surface plasmon resonance with recombinant iNKT TCRs and different ligand-CD1d complexes, we demonstrate that the CDR3beta sequence strongly impacts on the iNKT TCR affinity to CD1d, independent of the loaded CD1d ligand. Collectively our data reveal a crucial role for CDR3beta for the function of human iNKT cells by tuning the overall affinity of the iNKT TCR to CD1d. This mechanism is relatively independent of the bound CD1d ligand and thus forms the basis of an inherent, CDR3beta dependent functional hierarchy of human iNKT cells.
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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.