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| <StructureSection load='6vtc' size='340' side='right'caption='[[6vtc]], [[Resolution|resolution]] 1.83Å' scene=''> | | <StructureSection load='6vtc' size='340' side='right'caption='[[6vtc]], [[Resolution|resolution]] 1.83Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
| <table><tr><td colspan='2'>[[6vtc]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VTC OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6VTC FirstGlance]. <br> | | <table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6VTC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6VTC FirstGlance]. <br> |
| </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6vqo|6vqo]], [[6vr1|6vr1]], [[6vr5|6vr5]], [[6vrm|6vrm]], [[6vrn|6vrn]]</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]] 1.83Å</td></tr> |
| <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6vtc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vtc OCA], [http://pdbe.org/6vtc PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6vtc RCSB], [http://www.ebi.ac.uk/pdbsum/6vtc PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6vtc ProSAT]</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=6vtc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6vtc OCA], [https://pdbe.org/6vtc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6vtc RCSB], [https://www.ebi.ac.uk/pdbsum/6vtc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6vtc ProSAT]</span></td></tr> |
| </table> | | </table> |
| <div style="background-color:#fffaf0;">
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| == Publication Abstract from PubMed ==
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| Adoptive cell therapy (ACT) with tumor-specific T cells can mediate cancer regression. The main target of tumor-specific T cells are neoantigens arising from mutations in self-proteins. Although the majority of cancer neoantigens are unique to each patient, and therefore not broadly useful for ACT, some are shared. We studied oligoclonal T-cell receptors (TCRs) that recognize a shared neoepitope arising from a driver mutation in the p53 oncogene (p53R175H) presented by HLA-A2. Here we report structures of wild-type and mutant p53-HLA-A2 ligands, as well as structures of three tumor-specific TCRs bound to p53R175H-HLA-A2. These structures reveal how a driver mutation in p53 rendered a self-peptide visible to T cells. The TCRs employ structurally distinct strategies that are highly focused on the mutation to discriminate between mutant and wild-type p53. The TCR-p53R175H-HLA-A2 complexes provide a framework for designing TCRs to improve potency for ACT without sacrificing specificity.
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| Structural basis for oligoclonal T cell recognition of a shared p53 cancer neoantigen.,Wu D, Gallagher DT, Gowthaman R, Pierce BG, Mariuzza RA Nat Commun. 2020 Jun 9;11(1):2908. doi: 10.1038/s41467-020-16755-y. PMID:32518267<ref>PMID:32518267</ref>
| | ==See Also== |
| | | *[[T-cell receptor 3D structures|T-cell receptor 3D structures]] |
| From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| </div>
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| <div class="pdbe-citations 6vtc" style="background-color:#fffaf0;"></div>
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| == References == | |
| <references/>
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| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
| [[Category: Human]]
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| [[Category: Large Structures]] | | [[Category: Large Structures]] |
| [[Category: Gallagher, D T]] | | [[Category: Gallagher DT]] |
| [[Category: Gowthaman, R]] | | [[Category: Gowthaman R]] |
| [[Category: Mariuzza, R A]] | | [[Category: Mariuzza RA]] |
| [[Category: Pierce, B G]] | | [[Category: Pierce BG]] |
| [[Category: Wu, D]] | | [[Category: Wu D]] |
| [[Category: Adoptive cell therapy]]
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| [[Category: Hla]]
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| [[Category: Immune system]]
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| [[Category: Mhc]]
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| [[Category: Tcr complex]]
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