ArticleThe Journal of experimental medicine2021
CD1a selectively captures endogenous cellular lipids that broadly block T cell response.
Article in The Journal of experimental medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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
33 citing papers in PubMed, 46 citations in OpenAlex.
- Sideways lipid presentation by the antigen-presenting molecule CD1c.Nature communications · 2025Article
- γδ T cell receptor recognition of CD1d in a lipid-independent manner.Nature communications · 2025Article
- Sideways lipid presentation by the antigen-presenting molecule CD1c.bioRxiv : the preprint server for biology · 2025Article
- CD1a and Lipids as Mediators of T Cell Activation in the Skin.The Journal of investigative dermatology · 2025Review
- Post-Translational Modified Neoantigens in Autoimmune Diseases: Challenges of Immune Tolerance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- CD1-restricted T cells: are unconventional allies the key to future TB vaccines?Frontiers in immunology · 2025Review
- The distinctive signature of regulatory CD4 T cells committed in the human thymus.Frontiers in immunology · 2025Article
- Optimizing iNKT-driven immune responses against cancer by modulating CD1d in tumor and antigen presenting cells.Clinical immunology (Orlando, Fla.) · 2024Review
- Direct recognition of an intact foreign protein by an αβ T cell receptor.Nature communications · 2024Article
- 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
- A structural perspective of how T cell receptors recognize the CD1 family of lipid antigen-presenting molecules.The Journal of biological chemistry · 2024Review
- Protein Haptenation and Its Role in Allergy.Chemical research in toxicology · 2024Review
- CD1a and skin T cells: a pathway for therapeutic intervention.Clinical and experimental dermatology · 2024Review
- Human Skin T Cells Express Conserved T-Cell Receptors that Cross-React with Staphylococcal Superantigens and CD1a.The Journal of investigative dermatology · 2024Article
- Insights into the CD1 lipidome.Frontiers in immunology · 2024Article
- Integrated Analysis of CD1A Immune Infiltration and Competing Endogenous RNA Networks in COAD.International journal of general medicine · 2024Article
- Keratinocyte-derived small extracellular vesicles supply antigens for CD1a-resticted T cells and promote their type 2 bias in the context of filaggrin insufficiency.Frontiers in immunology · 2024Article
- Article
- CD1a and bound lipids drive T-cell responses in human skin disease.European journal of immunology · 2023Review
- Transcriptome alterations in peripheral blood B cells of patients with multiple sclerosis receiving immune reconstitution therapy.Journal of neuroinflammation · 2023Article
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Authors and funding
18 authors at 6 institutions in 3 countries.
Funding
Abstract
We optimized lipidomics methods to broadly detect endogenous lipids bound to cellular CD1a proteins. Whereas membrane phospholipids dominate in cells, CD1a preferentially captured sphingolipids, especially a C42, doubly unsaturated sphingomyelin (42:2 SM). The natural 42:2 SM but not the more common 34:1 SM blocked CD1a tetramer binding to T cells in all human subjects tested. Thus, cellular CD1a selectively captures a particular endogenous lipid that broadly blocks its binding to TCRs. Crystal structures show that the short cellular SMs stabilized a triad of surface residues to remain flush with CD1a, but the longer lipids forced the phosphocholine group to ride above the display platform to hinder TCR approach. Whereas nearly all models emphasize antigen-mediated T cell activation, we propose that the CD1a system has intrinsic autoreactivity and is negatively regulated by natural endogenous inhibitors selectively bound in its cleft. Further, the detailed chemical structures of natural blockers could guide future design of therapeutic blockers of CD1a response.
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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.