8cmc

Human Leukocyte Antigen class II allotype DR1 presenting SARS-CoV-2 Spike peptide S511-530

spinqualitylabelsall models 8cmc, resolution 1.42Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 8cmc is a 3 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 1.42Å Ligands: EDO, MES, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Publication Abstract from PubMed CD4(+) T cells recognize a broad range of peptide epitopes of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which contribute to immune memory and limit COVID-19 disease. We demonstrate that the immunogenicity of SARS-CoV-2 peptides, in the context of the model allotype HLA-DR1, does not correlate with their binding affinity to the HLA heterodimer. Analyzing six epitopes, some with very low binding affinity, we solve X-ray crystallographic structures of each bound to HLA-DR1. Further structural definitions reveal the precise molecular impact of viral variant mutations on epitope presentation. Omicron escaped ancestral SARS-CoV-2 immunity to two epitopes through two distinct mechanisms: (1) mutations to TCR-facing epitope positions and (2) a mechanism whereby a single amino acid substitution caused a register shift within the HLA binding groove, completely altering the peptide-HLA structure. This HLA-II-specific paradigm of immune escape highlights how CD4(+) T cell memory is finely poised at the level of peptide-HLA-II presentation. Structural definition of HLA class II-presented SARS-CoV-2 epitopes reveals a mechanism to escape pre-existing CD4(+) T cell immunity.,Chen Y, Mason GH, Scourfield DO, Greenshields-Watson A, Haigh TA, Sewell AK, Long HM, Gallimore AM, Rizkallah P, MacLachlan BJ, Godkin A Cell Rep. 2023 Aug 29;42(8):112827. doi: 10.1016/j.celrep.2023.112827. Epub 2023 , Jul 19. PMID:37471227 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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