8CMI

Human Leukocyte Antigen class II allotype DR1 presenting SARS-CoV-2 Omicron (BA.1) Spike peptide S761-775

8CMI の概要

• エントリーDOI: 10.2210/pdb8cmi/pdb
• 分子名称: HLA class II histocompatibility antigen, DR alpha chain, Human leukocyte antigen DR beta chain allotype DR1 (DRB1*0101), Spike protein S2', ... (6 entities in total)
• 機能のキーワード: hla-ii, hla-dr, hla-dr1, human leukocyte antigen, major histocompatibility complex, major histocompatibility complex class 2, sars-cov-2, coronavirus, covid-19, spike, omicron, ba.1, immune escape, viral variants, immune system
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 9
• 化学式量合計: 137889.00

構造登録者

MacLachlan, B.J.,Mason, G.H.,Sourfield, D.O.,Godkin, A.J.,Rizkallah, P.J. (登録日: 2023-02-19, 公開日: 2023-07-26, 最終更新日: 2024-11-13)

主引用文献

Chen, Y.,Mason, G.H.,Scourfield, D.O.,Greenshields-Watson, A.,Haigh, T.A.,Sewell, A.K.,Long, H.M.,Gallimore, A.M.,Rizkallah, P.,MacLachlan, B.J.,Godkin, A.
Structural definition of HLA class II-presented SARS-CoV-2 epitopes reveals a mechanism to escape pre-existing CD4 + T cell immunity.
Cell Rep, 42:112827-112827, 2023

PubMed Abstract: 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.

PubMed: 37471227
DOI: 10.1016/j.celrep.2023.112827

実験手法

X-RAY DIFFRACTION (2.6 Å)