7n6d: Difference between revisions
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==HLA peptide complex== | |||
<StructureSection load='7n6d' size='340' side='right'caption='[[7n6d]], [[Resolution|resolution]] 2.30Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7n6d]] is a 12 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] and [https://en.wikipedia.org/wiki/Severe_acute_respiratory_syndrome_coronavirus_2 Severe acute respiratory syndrome coronavirus 2]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7N6D OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7N6D FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene></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=7n6d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7n6d OCA], [https://pdbe.org/7n6d PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7n6d RCSB], [https://www.ebi.ac.uk/pdbsum/7n6d PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7n6d ProSAT]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
CD8(+) T cells play an important role in vaccination and immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Although numerous SARS-CoV-2 CD8(+) T cell epitopes have been identified, the molecular basis underpinning T cell receptor (TCR) recognition of SARS-CoV-2-specific T cells remains unknown. The T cell response directed toward SARS-CoV-2 spike protein-derived S(269-277) peptide presented by the human leukocyte antigen (HLA)-A *02:01 allomorph (hereafter the HLA-A2(S269-277) epitope) is, to date, the most immunodominant SARS-CoV-2 epitope found in individuals bearing this allele. As HLA-A2(S269-277)-specific CD8(+) T cells utilize biased TRAV12 gene usage within the TCR alpha-chain, we sought to understand the molecular basis underpinning this TRAV12 dominance. We expressed four TRAV12(+) TCRs which bound the HLA-A2(S269-277) complex with low micromolar affinity and determined the crystal structure of the HLA-A2(S269-277) binary complex, and subsequently a ternary structure of the TRAV12(+) TCR complexed to HLA-A2(S269-277). We found that the TCR made extensive contacts along the entire length of the S(269-277) peptide, suggesting that the TRAV12(+) TCRs would be sensitive to sequence variation within this epitope. To examine this, we investigated cross-reactivity toward analogous peptides from existing SARS-CoV-2 variants and closely related coronaviruses. We show via surface plasmon resonance and tetramer studies that the TRAV12(+) T cell repertoire cross-reacts poorly with these analogous epitopes. Overall, we defined the structural basis underpinning biased TCR recognition of CD8(+) T cells directed at an immunodominant epitope and provide a framework for understanding TCR cross-reactivity toward viral variants within the S(269-277) peptide. | |||
Structural basis of biased T cell receptor recognition of an immunodominant HLA-A2 epitope of the SARS-CoV-2 spike protein.,Chaurasia P, Nguyen THO, Rowntree LC, Juno JA, Wheatley AK, Kent SJ, Kedzierska K, Rossjohn J, Petersen J J Biol Chem. 2021 Sep;297(3):101065. doi: 10.1016/j.jbc.2021.101065. Epub 2021 , Aug 10. PMID:34384783<ref>PMID:34384783</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7n6d" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Beta-2 microglobulin 3D structures|Beta-2 microglobulin 3D structures]] | |||
*[[MHC 3D structures|MHC 3D structures]] | |||
*[[MHC I 3D structures|MHC I 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Severe acute respiratory syndrome coronavirus 2]] | |||
[[Category: Chaurasia P]] | |||
[[Category: Petersen J]] | |||
[[Category: Rossjohn J]] |