5brz
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==MAGE-A3 reactive TCR in complex with MAGE-A3 in HLA-A1== | |
| + | <StructureSection load='5brz' size='340' side='right' caption='[[5brz]], [[Resolution|resolution]] 2.62Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[5brz]] is a 5 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5BRZ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5BRZ FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5bs0|5bs0]]</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=5brz FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5brz OCA], [http://pdbe.org/5brz PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5brz RCSB], [http://www.ebi.ac.uk/pdbsum/5brz PDBsum]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Defects in B2M are the cause of hypercatabolic hypoproteinemia (HYCATHYP) [MIM:[http://omim.org/entry/241600 241600]]. Affected individuals show marked reduction in serum concentrations of immunoglobulin and albumin, probably due to rapid degradation.<ref>PMID:16549777</ref> Note=Beta-2-microglobulin may adopt the fibrillar configuration of amyloid in certain pathologic states. The capacity to assemble into amyloid fibrils is concentration dependent. Persistently high beta(2)-microglobulin serum levels lead to amyloidosis in patients on long-term hemodialysis.<ref>PMID:3532124</ref> <ref>PMID:1336137</ref> <ref>PMID:7554280</ref> <ref>PMID:4586824</ref> <ref>PMID:8084451</ref> <ref>PMID:12119416</ref> <ref>PMID:12796775</ref> <ref>PMID:16901902</ref> <ref>PMID:16491088</ref> <ref>PMID:17646174</ref> <ref>PMID:18835253</ref> <ref>PMID:18395224</ref> <ref>PMID:19284997</ref> | ||
| + | == Function == | ||
| + | [[http://www.uniprot.org/uniprot/1A01_HUMAN 1A01_HUMAN]] Involved in the presentation of foreign antigens to the immune system. [[http://www.uniprot.org/uniprot/B2MG_HUMAN B2MG_HUMAN]] Component of the class I major histocompatibility complex (MHC). Involved in the presentation of peptide antigens to the immune system. | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Natural T-cell responses generally lack the potency to eradicate cancer. Enhanced affinity T-cell receptors (TCRs) provide an ideal approach to target cancer cells, with emerging clinical data showing significant promise. Nevertheless, the risk of off target reactivity remains a key concern, as exemplified in a recent clinical report describing fatal cardiac toxicity, following administration of MAGE-A3 specific TCR-engineered T-cells, mediated through cross-reactivity with an unrelated epitope from the Titin protein presented on cardiac tissue. Here, we investigated the structural mechanism enabling TCR cross-recognition of MAGE-A3 and Titin, and applied the resulting data to rationally design mutants with improved antigen discrimination, providing a proof-of-concept strategy for altering the fine specificity of a TCR towards an intended target antigen. This study represents the first example of direct molecular mimicry leading to clinically relevant fatal toxicity, mediated by a modified enhanced affinity TCR designed for cancer immunotherapy. Furthermore, these data demonstrate that self-antigens that are expressed at high levels on healthy tissue should be treated with extreme caution when designing immuno-therapeutics. | ||
| - | + | Direct molecular mimicry enables off-target cardiovascular toxicity by an enhanced affinity TCR designed for cancer immunotherapy.,Raman MC, Rizkallah PJ, Simmons R, Donnellan Z, Dukes J, Bossi G, Le Provost GS, Todorov P, Baston E, Hickman E, Mahon T, Hassan N, Vuidepot A, Sami M, Cole DK, Jakobsen BK Sci Rep. 2016 Jan 13;6:18851. doi: 10.1038/srep18851. PMID:26758806<ref>PMID:26758806</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 5brz" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Bossi, G]] | ||
| + | [[Category: Cole, D K]] | ||
| + | [[Category: Donnellan, Z]] | ||
| + | [[Category: Dukes, J]] | ||
| + | [[Category: Hassan, N]] | ||
| + | [[Category: Hickman, E]] | ||
| + | [[Category: Jakobsen, B K]] | ||
| + | [[Category: LeProvost, G]] | ||
| + | [[Category: LomaX, M]] | ||
| + | [[Category: Mahon, T]] | ||
[[Category: Oates, J]] | [[Category: Oates, J]] | ||
| - | [[Category: Raman, M | + | [[Category: Raman, M C.C]] |
| + | [[Category: Rizkallah, P J]] | ||
[[Category: Sami, M]] | [[Category: Sami, M]] | ||
| - | [[Category: Jakobsen, B.K]] | ||
| - | [[Category: Leprovost, G]] | ||
[[Category: Simmons, R]] | [[Category: Simmons, R]] | ||
| - | [[Category: | + | [[Category: Vuidepot, A]] |
| - | [[Category: | + | [[Category: Immune system]] |
| - | [[Category: | + | [[Category: Immuno pmhc tcr mage]] |
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Revision as of 15:05, 2 March 2016
MAGE-A3 reactive TCR in complex with MAGE-A3 in HLA-A1
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Categories: Bossi, G | Cole, D K | Donnellan, Z | Dukes, J | Hassan, N | Hickman, E | Jakobsen, B K | LeProvost, G | LomaX, M | Mahon, T | Oates, J | Raman, M C.C | Rizkallah, P J | Sami, M | Simmons, R | Vuidepot, A | Immune system | Immuno pmhc tcr mage
