Distinct CD1d docking strategies exhibited by diverse Type II NKT cell receptors
| Autor: | Dylan G.M. Smith, Spencer J. Williams, Dale I. Godfrey, Daniel G. Pellicci, Benjamin Cao, Satvika Burugupalli, Catarina F. Almeida, Onisha Patel, Srinivasan Sundararaj, Jamie Rossjohn, Manfred Brigl, Adam P Uldrich, Jérôme Le Nours, T. Praveena |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Receptors Antigen T-Cell alpha-beta General Physics and Astronomy Crystallography X-Ray Mice 0302 clinical medicine T-Lymphocyte Subsets Lymphocytes lcsh:Science Mice Knockout education.field_of_study Antigen Presentation Multidisciplinary biology Chemistry hemic and immune systems Natural killer T cell Flow Cytometry Cell biology Molecular Docking Simulation medicine.anatomical_structure CD1D lipids (amino acids peptides and proteins) Structural biology T cell Science Population Antigen presentation Receptors Antigen T-Cell Galactosylceramides chemical and pharmacologic phenomena Major histocompatibility complex General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Antigen medicine Animals education T-cell receptor General Chemistry Antimicrobial responses Protein Structure Tertiary 030104 developmental biology biology.protein Natural Killer T-Cells lcsh:Q Antigens CD1d Glycolipids MHC 030215 immunology |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-14 (2019) Nature Communications |
| ISSN: | 2041-1723 |
| Popis: | Type I and type II natural killer T (NKT) cells are restricted to the lipid antigen-presenting molecule CD1d. While we have an understanding of the antigen reactivity and function of type I NKT cells, our knowledge of type II NKT cells in health and disease remains unclear. Here we describe a population of type II NKT cells that recognise and respond to the microbial antigen, α-glucuronosyl-diacylglycerol (α-GlcADAG) presented by CD1d, but not the prototypical type I NKT cell agonist, α-galactosylceramide. Surprisingly, the crystal structure of a type II NKT TCR-CD1d-α-GlcADAG complex reveals a CD1d F’-pocket-docking mode that contrasts sharply with the previously determined A’-roof positioning of a sulfatide-reactive type II NKT TCR. Our data also suggest that diverse type II NKT TCRs directed against distinct microbial or mammalian lipid antigens adopt multiple recognition strategies on CD1d, thereby maximising the potential for type II NKT cells to detect different lipid antigens. Natural killer T (NKT) cells include type I that express semi-invariant T cell receptor (TCR), and type II that cover a broader repertoire. Here the authors describe the crystal structure of a type II NKT TCR complexed with CD1d/antigen to propose that type II NKT TCRs may adapt multiple CD1d docking modes to maximise antigen recognition efficacy. |
| Databáze: | OpenAIRE |
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