Structural highlights
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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chen Y, Mason GH, Scourfield DO, Greenshields-Watson A, Haigh TA, Sewell AK, Long HM, Gallimore AM, Rizkallah P, MacLachlan BJ, 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. 2023 Aug 29;42(8):112827. PMID:37471227 doi:10.1016/j.celrep.2023.112827
