7r7z: Difference between revisions
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=7r7z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r7z OCA], [https://pdbe.org/7r7z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r7z RCSB], [https://www.ebi.ac.uk/pdbsum/7r7z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r7z 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=7r7z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7r7z OCA], [https://pdbe.org/7r7z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7r7z RCSB], [https://www.ebi.ac.uk/pdbsum/7r7z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7r7z ProSAT]</span></td></tr> | ||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Cytotoxic-T-lymphocyte (CTL) mediated control of HIV-1 is enhanced by targeting highly networked epitopes in complex with human-leukocyte-antigen-class-I (HLA-I). However, the extent to which the presenting HLA allele contributes to this process is unknown. Here we examine the CTL response to QW9, a highly networked epitope presented by the disease-protective HLA-B57 and disease-neutral HLA-B53. Despite robust targeting of QW9 in persons expressing either allele, T cell receptor (TCR) cross-recognition of the naturally occurring variant QW9_S3T is consistently reduced when presented by HLA-B53 but not by HLA-B57. Crystal structures show substantial conformational changes from QW9-HLA to QW9_S3T-HLA by both alleles. The TCR-QW9-B53 ternary complex structure manifests how the QW9-B53 can elicit effective CTLs and suggests sterically hindered cross-recognition by QW9_S3T-B53. We observe populations of cross-reactive TCRs for B57, but not B53 and also find greater peptide-HLA stability for B57 in comparison to B53. These data demonstrate differential impacts of HLAs on TCR cross-recognition and antigen presentation of a naturally arising variant, with important implications for vaccine design. | |||
Molecular basis of differential HLA class I-restricted T cell recognition of a highly networked HIV peptide.,Li X, Singh NK, Collins DR, Ng R, Zhang A, Lamothe-Molina PA, Shahinian P, Xu S, Tan K, Piechocka-Trocha A, Urbach JM, Weber JK, Gaiha GD, Takou Mbah OC, Huynh T, Cheever S, Chen J, Birnbaum M, Zhou R, Walker BD, Wang JH Nat Commun. 2023 May 22;14(1):2929. doi: 10.1038/s41467-023-38573-8. PMID:37217466<ref>PMID:37217466</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7r7z" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[T-cell receptor 3D structures|T-cell receptor 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
Latest revision as of 16:57, 6 November 2024
Crystal structure of QW9-HLA-B*5301 specific T Cell Receptor, C3Crystal structure of QW9-HLA-B*5301 specific T Cell Receptor, C3
Structural highlights
Publication Abstract from PubMedCytotoxic-T-lymphocyte (CTL) mediated control of HIV-1 is enhanced by targeting highly networked epitopes in complex with human-leukocyte-antigen-class-I (HLA-I). However, the extent to which the presenting HLA allele contributes to this process is unknown. Here we examine the CTL response to QW9, a highly networked epitope presented by the disease-protective HLA-B57 and disease-neutral HLA-B53. Despite robust targeting of QW9 in persons expressing either allele, T cell receptor (TCR) cross-recognition of the naturally occurring variant QW9_S3T is consistently reduced when presented by HLA-B53 but not by HLA-B57. Crystal structures show substantial conformational changes from QW9-HLA to QW9_S3T-HLA by both alleles. The TCR-QW9-B53 ternary complex structure manifests how the QW9-B53 can elicit effective CTLs and suggests sterically hindered cross-recognition by QW9_S3T-B53. We observe populations of cross-reactive TCRs for B57, but not B53 and also find greater peptide-HLA stability for B57 in comparison to B53. These data demonstrate differential impacts of HLAs on TCR cross-recognition and antigen presentation of a naturally arising variant, with important implications for vaccine design. Molecular basis of differential HLA class I-restricted T cell recognition of a highly networked HIV peptide.,Li X, Singh NK, Collins DR, Ng R, Zhang A, Lamothe-Molina PA, Shahinian P, Xu S, Tan K, Piechocka-Trocha A, Urbach JM, Weber JK, Gaiha GD, Takou Mbah OC, Huynh T, Cheever S, Chen J, Birnbaum M, Zhou R, Walker BD, Wang JH Nat Commun. 2023 May 22;14(1):2929. doi: 10.1038/s41467-023-38573-8. PMID:37217466[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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