28il

P1-15 T-cell Receptor bound to HLA A*2402-NF9 pMHC complex

spinqualitylabelsall models 28il, resolution 3.10Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 28il is a 10 chain structure with sequence from Homo sapiens and Severe acute respiratory syndrome coronavirus 2. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 3.1Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function A0A411J078_HUMAN 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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