8CME

Human Leukocyte Antigen class II allotype DR1 presenting SARS-CoV-2 Membrane peptide M176-190

Summary for 8CME

• Entry DOI: 10.2210/pdb8cme/pdb
• Descriptor: HLA class II histocompatibility antigen, DR alpha chain, Human leukocyte antigen DR beta chain allotype DR1 (DRB1*0101), Membrane protein, ... (6 entities in total)
• Functional Keywords: hla-ii, hla-dr, hla-dr1, human leukocyte antigen, major histocompatibility complex, major histocompatibility complex class 2, sars-cov-2, coronavirus, covid-19, membrane, immune system
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 9
• Total formula weight: 136531.68

Authors

MacLachlan, B.J.,Mason, G.H.,Sourfield, D.O.,Godkin, A.J.,Rizkallah, P.J. (deposition date: 2023-02-19, release date: 2023-07-26, Last modification date: 2024-10-23)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.26 Å)