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| | ==Structure of the mouse CD1d-HS44-iNKT TCR complex== | | ==Structure of the mouse CD1d-HS44-iNKT TCR complex== |
| - | <StructureSection load='3rtq' size='340' side='right' caption='[[3rtq]], [[Resolution|resolution]] 2.80Å' scene=''> | + | <StructureSection load='3rtq' size='340' side='right'caption='[[3rtq]], [[Resolution|resolution]] 2.80Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3rtq]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RTQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RTQ FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3rtq]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3RTQ OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3RTQ FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=H4S:N-[(2S,3S,4R)-3,4-DIHYDROXY-1-{[(1S,2S,3R,4R,5S)-2,3,4,5-TETRAHYDROXYCYCLOHEXYL]AMINO}OCTADECAN-2-YL]HEXACOSANAMIDE'>H4S</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.8Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Cd1.1, CD1d, Cd1d1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]), B2m ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]), Valpha14 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus]), Vbeta8.2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=FUL:BETA-L-FUCOSE'>FUL</scene>, <scene name='pdbligand=H4S:N-[(2S,3S,4R)-3,4-DIHYDROXY-1-{[(1S,2S,3R,4R,5S)-2,3,4,5-TETRAHYDROXYCYCLOHEXYL]AMINO}OCTADECAN-2-YL]HEXACOSANAMIDE'>H4S</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3rtq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rtq OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rtq RCSB], [http://www.ebi.ac.uk/pdbsum/3rtq PDBsum]</span></td></tr> | + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3rtq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rtq OCA], [https://pdbe.org/3rtq PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3rtq RCSB], [https://www.ebi.ac.uk/pdbsum/3rtq PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3rtq ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/CD1D1_MOUSE CD1D1_MOUSE]] Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.<ref>PMID:11754812</ref> <ref>PMID:16314439</ref> <ref>PMID:16007091</ref> [[http://www.uniprot.org/uniprot/B2MG_MOUSE B2MG_MOUSE]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. | + | [https://www.uniprot.org/uniprot/CD1D1_MOUSE CD1D1_MOUSE] Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.<ref>PMID:11754812</ref> <ref>PMID:16314439</ref> <ref>PMID:16007091</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | </div> | | </div> |
| | + | <div class="pdbe-citations 3rtq" style="background-color:#fffaf0;"></div> |
| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Beta-2 microglobulin|Beta-2 microglobulin]] | + | *[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] |
| | *[[CD1|CD1]] | | *[[CD1|CD1]] |
| | == References == | | == References == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Yu, E D]] | + | [[Category: Yu ED]] |
| - | [[Category: Zajonc, D M]] | + | [[Category: Zajonc DM]] |
| - | [[Category: Antigen presentation]]
| + | |
| - | [[Category: Glycolipid]]
| + | |
| - | [[Category: Immune system]]
| + | |
| - | [[Category: Nkt cell]]
| + | |
| Structural highlights
Function
CD1D1_MOUSE Antigen-presenting protein that binds self and non-self glycolipids and presents them to T-cell receptors on natural killer T-cells.[1] [2] [3]
Publication Abstract from PubMed
Activation of type I NKT (iNKT) cells by CD1d-presented agonists is a potent immunotherapeutic tool. alpha-Galactosylceramide (alpha-GalCer) is the prototypic agonist, but its excessive potency with simultaneous production of both pro- and anti-inflammatory cytokines hampers its potential therapeutic use. In search for novel agonists, we have analyzed the structure and function of HS44, a synthetic aminocyclitolic ceramide analog designed to avoid unrestrained iNKT cell activation. HS44 is a weaker agonist compared with alpha-GalCer in vitro, although in vivo it induces robust IFN-gamma production, and highly reduced but still functional Th2 response. The characteristic cytokine storm produced upon alpha-GalCer activation was not induced. Consequently, HS44 induced a very efficient iNKT cell-dependent antitumoral response in B16 animal model. In addition, intranasal administration showed the capacity to induce lung inflammation and airway hyperreactivity, a cardinal asthma feature. Thus, HS44 is able to elicit functional Th1 or Th2 responses. Structural studies show that HS44 binds to CD1d with the same conformation as alpha-GalCer. The TCR binds to HS44 similarly as alpha-GalCer, but forms less contacts, thus explaining its weaker TCR affinity and, consequently, its weaker recognition by iNKT cells. The ability of this compound to activate an efficient, but not massive, tailored functional immune response makes it an attractive reagent for immune manipulation.
Structural and functional characterization of a novel nonglycosidic type I NKT agonist with immunomodulatory properties.,Kerzerho J, Yu ED, Barra CM, Alari-Pahisa E, Girardi E, Harrak Y, Lauzurica P, Llebaria A, Zajonc DM, Akbari O, Castano AR J Immunol. 2012 Mar 1;188(5):2254-65. Epub 2012 Feb 1. PMID:22301545[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Jayawardena-Wolf J, Benlagha K, Chiu YH, Mehr R, Bendelac A. CD1d endosomal trafficking is independently regulated by an intrinsic CD1d-encoded tyrosine motif and by the invariant chain. Immunity. 2001 Dec;15(6):897-908. PMID:11754812
- ↑ Zajonc DM, Maricic I, Wu D, Halder R, Roy K, Wong CH, Kumar V, Wilson IA. Structural basis for CD1d presentation of a sulfatide derived from myelin and its implications for autoimmunity. J Exp Med. 2005 Dec 5;202(11):1517-26. Epub 2005 Nov 28. PMID:16314439 doi:10.1084/jem.20051625
- ↑ Zajonc DM, Cantu C 3rd, Mattner J, Zhou D, Savage PB, Bendelac A, Wilson IA, Teyton L. Structure and function of a potent agonist for the semi-invariant natural killer T cell receptor. Nat Immunol. 2005 Aug;6(8):810-8. Epub 2005 Jul 10. PMID:16007091 doi:10.1038/ni1224
- ↑ Kerzerho J, Yu ED, Barra CM, Alari-Pahisa E, Girardi E, Harrak Y, Lauzurica P, Llebaria A, Zajonc DM, Akbari O, Castano AR. Structural and functional characterization of a novel nonglycosidic type I NKT agonist with immunomodulatory properties. J Immunol. 2012 Mar 1;188(5):2254-65. Epub 2012 Feb 1. PMID:22301545 doi:http://dx.doi.org/10.4049/jimmunol.1103049
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