tetano
Editor, Senior Moderator
Cell Rep
. 2023 Jul 18;42(8):112827.
doi: 10.1016/j.celrep.2023.112827. Online ahead of print. Structural definition of HLA class II-presented SARS-CoV-2 epitopes reveals a mechanism to escape pre-existing CD4[SUP]+[/SUP] T cell immunity
Yuan Chen[SUP] 1 [/SUP], Georgina H Mason[SUP] 1 [/SUP], D Oliver Scourfield[SUP] 1 [/SUP], Alexander Greenshields-Watson[SUP] 1 [/SUP], Tracey A Haigh[SUP] 2 [/SUP], Andrew K Sewell[SUP] 1 [/SUP], Heather M Long[SUP] 2 [/SUP], Awen M Gallimore[SUP] 1 [/SUP], Pierre Rizkallah[SUP] 1 [/SUP], Bruce J MacLachlan[SUP] 3 [/SUP], Andrew Godkin[SUP] 4 [/SUP]
Affiliations
CD4[SUP]+[/SUP] 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[SUP]+[/SUP] T cell memory is finely poised at the level of peptide-HLA-II presentation.
Keywords: CD4(+) T cells; COVID-19; CP: Immunology; HLA class II; SARS-CoV-2; T cells; antigen presentation; coronavirus; crystallography; immune escape; immune memory.
. 2023 Jul 18;42(8):112827.
doi: 10.1016/j.celrep.2023.112827. Online ahead of print. Structural definition of HLA class II-presented SARS-CoV-2 epitopes reveals a mechanism to escape pre-existing CD4[SUP]+[/SUP] T cell immunity
Yuan Chen[SUP] 1 [/SUP], Georgina H Mason[SUP] 1 [/SUP], D Oliver Scourfield[SUP] 1 [/SUP], Alexander Greenshields-Watson[SUP] 1 [/SUP], Tracey A Haigh[SUP] 2 [/SUP], Andrew K Sewell[SUP] 1 [/SUP], Heather M Long[SUP] 2 [/SUP], Awen M Gallimore[SUP] 1 [/SUP], Pierre Rizkallah[SUP] 1 [/SUP], Bruce J MacLachlan[SUP] 3 [/SUP], Andrew Godkin[SUP] 4 [/SUP]
Affiliations
- PMID: 37471227
- DOI: 10.1016/j.celrep.2023.112827
CD4[SUP]+[/SUP] 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[SUP]+[/SUP] T cell memory is finely poised at the level of peptide-HLA-II presentation.
Keywords: CD4(+) T cells; COVID-19; CP: Immunology; HLA class II; SARS-CoV-2; T cells; antigen presentation; coronavirus; crystallography; immune escape; immune memory.