View source for 28il


==P1-15 T-cell Receptor bound to HLA A*2402-NF9 pMHC complex==
<StructureSection load='28il' size='340' side='right'caption='[[28il]], [[Resolution|resolution]] 3.10&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[28il]] is a 10 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=28IL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=28IL 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]] 3.1&#8491;</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=28il FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=28il OCA], [https://pdbe.org/28il PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=28il RCSB], [https://www.ebi.ac.uk/pdbsum/28il PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=28il ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/A0A411J078_HUMAN A0A411J078_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cytotoxic T lymphocytes form a critical component of SARS-CoV-2 immunity by recognizing viral peptides bound to HLA class I molecules. Here, we identified the spike-derived peptide NYNYLYRLF448-456 (NF9) as the immunodominant HLA-A*24:02-restricted epitope in both convalescent and vaccinated donors. Across cohorts, A24/NF9-specific responses were dominated by public TCR motifs featuring TRAV12-1 paired with TRBJ2-7 and a conserved CDR3beta sequence (CASSXXXGYEQYF). Using a panel of 13 TCRs, we mapped recognition of single amino acid substitutions within NF9 and identified residue 5 (L452) as the principal determinant of escape. The L452R substitution, characteristic of the Delta variant, abolished recognition across all tested TCRs despite preserved HLA binding. Crystallography of a representative public TCR (P1-15) revealed that mutation at position-5 reoriented the peptide within HLA-A*24:02, flipping the adjacent Y453 side chain into the peptide-binding groove and eliminating the dominant TCR contact. This position-5-driven conformational switch provided a structural mechanism for universal loss of NF9 recognition by HLA-A*24:02-restricted T cells. Consistent with this, Delta-infected convalescents failed to mount de novo NF9-5R-specific responses while retaining responses to the conserved A24/QI9 spike epitope. Together, these findings defined the basis of A24/NF9 recognition and showed how 1 mutation remodeled peptide presentation to abrogate TCR responses.

Position-5-driven reorientation of an immunodominant HLA-A*24:02 SARS-CoV-2 epitope drives universal T cell escape.,Nakama T, Wall A, Dolton G, Tan LR, Thomas H, Hamana H, Aritsu Y, Tan TS, Toyoda M, Goto Y, Li H, Kitamatsu M, Udaka K, Miyashita Y, Oshiumi H, Nakamura K, Nagasaki Y, Minami R, Nakata H, Rizkallah PJ, Kishi H, Ueno T, Sewell AK, Motozono C JCI Insight. 2026 Mar 17;11(9):e202235. doi: 10.1172/jci.insight.202235. , eCollection 2026 May 8. PMID:41842944<ref>PMID:41842944</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 28il" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Severe acute respiratory syndrome coronavirus 2]]
[[Category: Fuller A]]
[[Category: Motozono C]]
[[Category: Rizkallah PJ]]
[[Category: Sewell AK]]
[[Category: Wall A]]