tetano
Editor, Senior Moderator
Immunology
. 2022 Feb 10.
doi: 10.1111/imm.13451. Online ahead of print.
HLA-dependent variation in SARS-CoV-2 CD8+ T cell cross-reactivity with human coronaviruses
Paul R Buckley[SUP] 1 2 [/SUP], Chloe H Lee[SUP] 1 2 [/SUP], Mariana Pereira Pinho[SUP] 1 [/SUP], Rosana Ottakandathil Babu[SUP] 1 2 [/SUP], Jeongmin Woo[SUP] 1 2 [/SUP], Agne Antanaviciute[SUP] 1 2 [/SUP], Alison Simmons[SUP] 1 [/SUP], Graham Ogg[SUP] 1 [/SUP], Hashem Koohy[SUP] 1 2 [/SUP]
Affiliations
Abstract
The conditions and extent of cross-protective immunity between SARS-CoV-2 and common-cold human coronaviruses HCoVs remain open despite several reports of pre-existing T cell immunity to SARS-CoV-2 in individuals without prior exposure. Using a pool of functionally evaluated SARS-CoV-2 peptides, we report a map of 126 immunogenic peptides with high similarity to 285 MHC-presented peptides from at least one HCoV. Employing this map of SARS-CoV-2-non-homologous and homologous immunogenic peptides, we observe several immunogenic peptides with high similarity to human proteins, some of which have been reported to have elevated expression in severe COVID-19 patients. After combining our map with SARS-CoV-2-specific TCR repertoire data from COVID-19 patients and healthy controls, we show that public repertoires for the majority of convalescent patients are dominated by TCRs cognate to non-homologous SARS-CoV-2 peptides. We find that for a subset of patients, >50% of their public SARS-CoV-2-specific repertoires consist of TCRs cognate to homologous SARS-CoV-2-HCoV peptides. Further analysis suggests that this skewed distribution of TCRs cognate to homologous or non-homologous peptides in COVID-19 patients is likely to be HLA-dependent. Finally, we provide 10 SARS-CoV-2 peptides with known cognate TCRs that are conserved across multiple coronaviruses and are predicted to be recognised by a high proportion of the global population. These findings may have important implications for COVID-19 heterogeneity, vaccine-induced immune responses, and robustness of immunity to SARS-CoV-2 and its variants.
Keywords: CD8 T cells; Coronavirus; Immunogenicity; SARS-CoV-2; T cell cross-reactivity; T cell response; peptide presentation; pre-existing T cell immunity.
. 2022 Feb 10.
doi: 10.1111/imm.13451. Online ahead of print.
HLA-dependent variation in SARS-CoV-2 CD8+ T cell cross-reactivity with human coronaviruses
Paul R Buckley[SUP] 1 2 [/SUP], Chloe H Lee[SUP] 1 2 [/SUP], Mariana Pereira Pinho[SUP] 1 [/SUP], Rosana Ottakandathil Babu[SUP] 1 2 [/SUP], Jeongmin Woo[SUP] 1 2 [/SUP], Agne Antanaviciute[SUP] 1 2 [/SUP], Alison Simmons[SUP] 1 [/SUP], Graham Ogg[SUP] 1 [/SUP], Hashem Koohy[SUP] 1 2 [/SUP]
Affiliations
- PMID: 35143694
- DOI: 10.1111/imm.13451
Abstract
The conditions and extent of cross-protective immunity between SARS-CoV-2 and common-cold human coronaviruses HCoVs remain open despite several reports of pre-existing T cell immunity to SARS-CoV-2 in individuals without prior exposure. Using a pool of functionally evaluated SARS-CoV-2 peptides, we report a map of 126 immunogenic peptides with high similarity to 285 MHC-presented peptides from at least one HCoV. Employing this map of SARS-CoV-2-non-homologous and homologous immunogenic peptides, we observe several immunogenic peptides with high similarity to human proteins, some of which have been reported to have elevated expression in severe COVID-19 patients. After combining our map with SARS-CoV-2-specific TCR repertoire data from COVID-19 patients and healthy controls, we show that public repertoires for the majority of convalescent patients are dominated by TCRs cognate to non-homologous SARS-CoV-2 peptides. We find that for a subset of patients, >50% of their public SARS-CoV-2-specific repertoires consist of TCRs cognate to homologous SARS-CoV-2-HCoV peptides. Further analysis suggests that this skewed distribution of TCRs cognate to homologous or non-homologous peptides in COVID-19 patients is likely to be HLA-dependent. Finally, we provide 10 SARS-CoV-2 peptides with known cognate TCRs that are conserved across multiple coronaviruses and are predicted to be recognised by a high proportion of the global population. These findings may have important implications for COVID-19 heterogeneity, vaccine-induced immune responses, and robustness of immunity to SARS-CoV-2 and its variants.
Keywords: CD8 T cells; Coronavirus; Immunogenicity; SARS-CoV-2; T cell cross-reactivity; T cell response; peptide presentation; pre-existing T cell immunity.