3ws3: Difference between revisions
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==Crystal Structure of H-2D in complex with an insulin derived peptide== | ==Crystal Structure of H-2D in complex with an insulin derived peptide== | ||
<StructureSection load='3ws3' size='340' side='right' caption='[[3ws3]], [[Resolution|resolution]] 2.33Å' scene=''> | <StructureSection load='3ws3' size='340' side='right'caption='[[3ws3]], [[Resolution|resolution]] 2.33Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[3ws3]] is a 6 chain structure with sequence from [ | <table><tr><td colspan='2'>[[3ws3]] is a 6 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=3WS3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3WS3 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.335Å</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=3ws3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3ws3 OCA], [https://pdbe.org/3ws3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3ws3 RCSB], [https://www.ebi.ac.uk/pdbsum/3ws3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3ws3 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</table> | </table> | ||
== Function == | == Function == | ||
[ | [https://www.uniprot.org/uniprot/HA11_MOUSE HA11_MOUSE] Involved in the presentation of foreign antigens to the immune system. | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Self-reactive T cells must escape thymic negative selection to mediate pathogenic autoimmunity. In the NOD mouse model of autoimmune diabetes, several beta cell-cytotoxic CD8 T cell populations are known, with the most aggressive of these represented by AI4, a T cell clone with promiscuous Ag-recognition characteristics. We identified a long-elusive beta cell-specific ligand for AI4 as an unusually short H-2D(b)-binding 7-mer peptide lacking a C-terminal anchor residue and derived from the insulin A chain (InsA14-20). Crystallography reveals that compensatory mechanisms permit peptides lacking a C-terminal anchor to bind sufficiently to the MHC to enable destructive T cell responses, yet allow cognate T cells to avoid negative selection. InsA14-20 shares two solvent-exposed residues with previously identified AI4 ligands, providing a structural explanation for AI4's promiscuity. Detection of AI4-like T cells, using mimotopes of InsA14-20 with improved H-2D(b)-binding characteristics, establishes the AI4-like T cell population as a consistent feature of the islet infiltrates of NOD mice. Our work establishes undersized peptides as previously unrecognized targets of autoreactive CD8 T cells and presents a strategy for their further exploration as Ags in autoimmune disease. | |||
Compensatory mechanisms allow undersized anchor-deficient class I MHC ligands to mediate pathogenic autoreactive T cell responses.,Lamont D, Mukherjee G, Kumar PR, Samanta D, McPhee CG, Kay TW, Almo SC, DiLorenzo TP, Serreze DV J Immunol. 2014 Sep 1;193(5):2135-46. doi: 10.4049/jimmunol.1400997. Epub 2014, Jul 25. PMID:25063871<ref>PMID:25063871</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 3ws3" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] | |||
*[[Beta-lactamase 3D structures|Beta-lactamase 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: | [[Category: Almo SC]] | ||
[[Category: | [[Category: DiLorenzo TP]] | ||
[[Category: | [[Category: Immune Function Network]] | ||
[[Category: | [[Category: Kumar PR]] | ||
[[Category: | [[Category: Mukherjee G]] | ||
[[Category: Samanta | [[Category: Samanta D]] | ||
Latest revision as of 16:24, 8 November 2023
Crystal Structure of H-2D in complex with an insulin derived peptideCrystal Structure of H-2D in complex with an insulin derived peptide
Structural highlights
FunctionHA11_MOUSE Involved in the presentation of foreign antigens to the immune system. Publication Abstract from PubMedSelf-reactive T cells must escape thymic negative selection to mediate pathogenic autoimmunity. In the NOD mouse model of autoimmune diabetes, several beta cell-cytotoxic CD8 T cell populations are known, with the most aggressive of these represented by AI4, a T cell clone with promiscuous Ag-recognition characteristics. We identified a long-elusive beta cell-specific ligand for AI4 as an unusually short H-2D(b)-binding 7-mer peptide lacking a C-terminal anchor residue and derived from the insulin A chain (InsA14-20). Crystallography reveals that compensatory mechanisms permit peptides lacking a C-terminal anchor to bind sufficiently to the MHC to enable destructive T cell responses, yet allow cognate T cells to avoid negative selection. InsA14-20 shares two solvent-exposed residues with previously identified AI4 ligands, providing a structural explanation for AI4's promiscuity. Detection of AI4-like T cells, using mimotopes of InsA14-20 with improved H-2D(b)-binding characteristics, establishes the AI4-like T cell population as a consistent feature of the islet infiltrates of NOD mice. Our work establishes undersized peptides as previously unrecognized targets of autoreactive CD8 T cells and presents a strategy for their further exploration as Ags in autoimmune disease. Compensatory mechanisms allow undersized anchor-deficient class I MHC ligands to mediate pathogenic autoreactive T cell responses.,Lamont D, Mukherjee G, Kumar PR, Samanta D, McPhee CG, Kay TW, Almo SC, DiLorenzo TP, Serreze DV J Immunol. 2014 Sep 1;193(5):2135-46. doi: 10.4049/jimmunol.1400997. Epub 2014, Jul 25. PMID:25063871[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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