Parallel detection of SARS‐CoV‐2 epitopes reveals dynamic immunodominance profiles of CD8+ T memory cells in convalescent COVID‐19 donors
Abstract Objectives High‐magnitude CD8+ T cell responses are associated with mild COVID‐19 disease; however, the underlying characteristics that define CD8+ T cell‐mediated protection are not well understood. The antigenic breadth and the immunodominance hierarchies of epitope‐specific CD8+ T cells...
| Main Authors: | , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2022-01-01
|
| Series: | Clinical & Translational Immunology |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cti2.1423 |
| _version_ | 1811257581879951360 |
|---|---|
| author | Jet van denDijssel Ruth R Hagen Rivka deJongh Maurice Steenhuis Theo Rispens Dionne M Geerdes Juk Yee Mok Angela HM Kragten Mariël C Duurland Niels JM Verstegen S Marieke vanHam Wim JE vanEsch Klaas PJM vanGisbergen Pleun Hombrink Anja tenBrinke Carolien E van deSandt |
| author_facet | Jet van denDijssel Ruth R Hagen Rivka deJongh Maurice Steenhuis Theo Rispens Dionne M Geerdes Juk Yee Mok Angela HM Kragten Mariël C Duurland Niels JM Verstegen S Marieke vanHam Wim JE vanEsch Klaas PJM vanGisbergen Pleun Hombrink Anja tenBrinke Carolien E van deSandt |
| author_sort | Jet van denDijssel |
| collection | DOAJ |
| description | Abstract Objectives High‐magnitude CD8+ T cell responses are associated with mild COVID‐19 disease; however, the underlying characteristics that define CD8+ T cell‐mediated protection are not well understood. The antigenic breadth and the immunodominance hierarchies of epitope‐specific CD8+ T cells remain largely unexplored and are essential for the development of next‐generation broad‐protective vaccines. This study identified a broad spectrum of conserved SARS‐CoV‐2 CD8+ T cell epitopes and defined their respective immunodominance and phenotypic profiles following SARS‐CoV‐2 infection. Methods CD8+ T cells from 51 convalescent COVID‐19 donors were analysed for their ability to recognise 133 predicted and previously described SARS‐CoV‐2‐derived peptides restricted by 11 common HLA class I allotypes using heterotetramer combinatorial coding, which combined with phenotypic markers allowed in‐depth ex vivo profiling of CD8+ T cell responses at quantitative and phenotypic levels. Results A comprehensive panel of 49 mostly conserved SARS‐CoV‐2‐specific CD8+ T cell epitopes, including five newly identified low‐magnitude epitopes, was established. We confirmed the immunodominance of HLA‐A*01:01/ORF1ab1637–1646 and B*07:02/N105–113 and identified B*35:01/N325–333 as a third epitope with immunodominant features. The magnitude of subdominant epitope responses, including A*03:01/N361–369 and A*02:01/S269–277, depended on the donors' HLA‐I context. All epitopes expressed prevalent memory phenotypes, with the highest memory frequencies in severe COVID‐19 donors. Conclusion SARS‐CoV‐2 infection induces a predominant CD8+ T memory response directed against a broad spectrum of conserved SARS‐CoV‐2 epitopes, which likely contributes to long‐term protection against severe disease. The observed immunodominance hierarchy emphasises the importance of T cell epitopes derived from nonspike proteins to the overall protective and cross‐reactive immune response, which could aid future vaccine strategies. |
| first_indexed | 2024-04-12T17:59:43Z |
| format | Article |
| id | doaj.art-d9b148eb22f04368b74c19967cb566df |
| institution | Directory Open Access Journal |
| issn | 2050-0068 |
| language | English |
| last_indexed | 2024-04-12T17:59:43Z |
| publishDate | 2022-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Clinical & Translational Immunology |
| spelling | doaj.art-d9b148eb22f04368b74c19967cb566df2022-12-22T03:22:12ZengWileyClinical & Translational Immunology2050-00682022-01-011110n/an/a10.1002/cti2.1423Parallel detection of SARS‐CoV‐2 epitopes reveals dynamic immunodominance profiles of CD8+ T memory cells in convalescent COVID‐19 donorsJet van denDijssel0Ruth R Hagen1Rivka deJongh2Maurice Steenhuis3Theo Rispens4Dionne M Geerdes5Juk Yee Mok6Angela HM Kragten7Mariël C Duurland8Niels JM Verstegen9S Marieke vanHam10Wim JE vanEsch11Klaas PJM vanGisbergen12Pleun Hombrink13Anja tenBrinke14Carolien E van deSandt15Department of Hematopoiesis Sanquin Research Amsterdam The NetherlandsDepartment of Hematopoiesis Sanquin Research Amsterdam The NetherlandsLandsteiner Laboratory Amsterdam UMC location University of Amsterdam Amsterdam The NetherlandsLandsteiner Laboratory Amsterdam UMC location University of Amsterdam Amsterdam The NetherlandsLandsteiner Laboratory Amsterdam UMC location University of Amsterdam Amsterdam The NetherlandsSanquin Reagents B.V. Amsterdam The NetherlandsSanquin Reagents B.V. Amsterdam The NetherlandsSanquin Reagents B.V. Amsterdam The NetherlandsLandsteiner Laboratory Amsterdam UMC location University of Amsterdam Amsterdam The NetherlandsLandsteiner Laboratory Amsterdam UMC location University of Amsterdam Amsterdam The NetherlandsLandsteiner Laboratory Amsterdam UMC location University of Amsterdam Amsterdam The NetherlandsSanquin Reagents B.V. Amsterdam The NetherlandsDepartment of Hematopoiesis Sanquin Research Amsterdam The NetherlandsDepartment of Hematopoiesis Sanquin Research Amsterdam The NetherlandsLandsteiner Laboratory Amsterdam UMC location University of Amsterdam Amsterdam The NetherlandsDepartment of Hematopoiesis Sanquin Research Amsterdam The NetherlandsAbstract Objectives High‐magnitude CD8+ T cell responses are associated with mild COVID‐19 disease; however, the underlying characteristics that define CD8+ T cell‐mediated protection are not well understood. The antigenic breadth and the immunodominance hierarchies of epitope‐specific CD8+ T cells remain largely unexplored and are essential for the development of next‐generation broad‐protective vaccines. This study identified a broad spectrum of conserved SARS‐CoV‐2 CD8+ T cell epitopes and defined their respective immunodominance and phenotypic profiles following SARS‐CoV‐2 infection. Methods CD8+ T cells from 51 convalescent COVID‐19 donors were analysed for their ability to recognise 133 predicted and previously described SARS‐CoV‐2‐derived peptides restricted by 11 common HLA class I allotypes using heterotetramer combinatorial coding, which combined with phenotypic markers allowed in‐depth ex vivo profiling of CD8+ T cell responses at quantitative and phenotypic levels. Results A comprehensive panel of 49 mostly conserved SARS‐CoV‐2‐specific CD8+ T cell epitopes, including five newly identified low‐magnitude epitopes, was established. We confirmed the immunodominance of HLA‐A*01:01/ORF1ab1637–1646 and B*07:02/N105–113 and identified B*35:01/N325–333 as a third epitope with immunodominant features. The magnitude of subdominant epitope responses, including A*03:01/N361–369 and A*02:01/S269–277, depended on the donors' HLA‐I context. All epitopes expressed prevalent memory phenotypes, with the highest memory frequencies in severe COVID‐19 donors. Conclusion SARS‐CoV‐2 infection induces a predominant CD8+ T memory response directed against a broad spectrum of conserved SARS‐CoV‐2 epitopes, which likely contributes to long‐term protection against severe disease. The observed immunodominance hierarchy emphasises the importance of T cell epitopes derived from nonspike proteins to the overall protective and cross‐reactive immune response, which could aid future vaccine strategies.https://doi.org/10.1002/cti2.1423CD8+ T cellsconvalescenceepitopesimmunodominanceinfectionSARS‐CoV‐2 |
| spellingShingle | Jet van denDijssel Ruth R Hagen Rivka deJongh Maurice Steenhuis Theo Rispens Dionne M Geerdes Juk Yee Mok Angela HM Kragten Mariël C Duurland Niels JM Verstegen S Marieke vanHam Wim JE vanEsch Klaas PJM vanGisbergen Pleun Hombrink Anja tenBrinke Carolien E van deSandt Parallel detection of SARS‐CoV‐2 epitopes reveals dynamic immunodominance profiles of CD8+ T memory cells in convalescent COVID‐19 donors Clinical & Translational Immunology CD8+ T cells convalescence epitopes immunodominance infection SARS‐CoV‐2 |
| title | Parallel detection of SARS‐CoV‐2 epitopes reveals dynamic immunodominance profiles of CD8+ T memory cells in convalescent COVID‐19 donors |
| title_full | Parallel detection of SARS‐CoV‐2 epitopes reveals dynamic immunodominance profiles of CD8+ T memory cells in convalescent COVID‐19 donors |
| title_fullStr | Parallel detection of SARS‐CoV‐2 epitopes reveals dynamic immunodominance profiles of CD8+ T memory cells in convalescent COVID‐19 donors |
| title_full_unstemmed | Parallel detection of SARS‐CoV‐2 epitopes reveals dynamic immunodominance profiles of CD8+ T memory cells in convalescent COVID‐19 donors |
| title_short | Parallel detection of SARS‐CoV‐2 epitopes reveals dynamic immunodominance profiles of CD8+ T memory cells in convalescent COVID‐19 donors |
| title_sort | parallel detection of sars cov 2 epitopes reveals dynamic immunodominance profiles of cd8 t memory cells in convalescent covid 19 donors |
| topic | CD8+ T cells convalescence epitopes immunodominance infection SARS‐CoV‐2 |
| url | https://doi.org/10.1002/cti2.1423 |
| work_keys_str_mv | AT jetvandendijssel paralleldetectionofsarscov2epitopesrevealsdynamicimmunodominanceprofilesofcd8tmemorycellsinconvalescentcovid19donors AT ruthrhagen paralleldetectionofsarscov2epitopesrevealsdynamicimmunodominanceprofilesofcd8tmemorycellsinconvalescentcovid19donors AT rivkadejongh paralleldetectionofsarscov2epitopesrevealsdynamicimmunodominanceprofilesofcd8tmemorycellsinconvalescentcovid19donors AT mauricesteenhuis paralleldetectionofsarscov2epitopesrevealsdynamicimmunodominanceprofilesofcd8tmemorycellsinconvalescentcovid19donors AT theorispens paralleldetectionofsarscov2epitopesrevealsdynamicimmunodominanceprofilesofcd8tmemorycellsinconvalescentcovid19donors AT dionnemgeerdes paralleldetectionofsarscov2epitopesrevealsdynamicimmunodominanceprofilesofcd8tmemorycellsinconvalescentcovid19donors AT jukyeemok paralleldetectionofsarscov2epitopesrevealsdynamicimmunodominanceprofilesofcd8tmemorycellsinconvalescentcovid19donors AT angelahmkragten paralleldetectionofsarscov2epitopesrevealsdynamicimmunodominanceprofilesofcd8tmemorycellsinconvalescentcovid19donors AT marielcduurland paralleldetectionofsarscov2epitopesrevealsdynamicimmunodominanceprofilesofcd8tmemorycellsinconvalescentcovid19donors AT nielsjmverstegen paralleldetectionofsarscov2epitopesrevealsdynamicimmunodominanceprofilesofcd8tmemorycellsinconvalescentcovid19donors AT smariekevanham paralleldetectionofsarscov2epitopesrevealsdynamicimmunodominanceprofilesofcd8tmemorycellsinconvalescentcovid19donors AT wimjevanesch paralleldetectionofsarscov2epitopesrevealsdynamicimmunodominanceprofilesofcd8tmemorycellsinconvalescentcovid19donors AT klaaspjmvangisbergen paralleldetectionofsarscov2epitopesrevealsdynamicimmunodominanceprofilesofcd8tmemorycellsinconvalescentcovid19donors AT pleunhombrink paralleldetectionofsarscov2epitopesrevealsdynamicimmunodominanceprofilesofcd8tmemorycellsinconvalescentcovid19donors AT anjatenbrinke paralleldetectionofsarscov2epitopesrevealsdynamicimmunodominanceprofilesofcd8tmemorycellsinconvalescentcovid19donors AT carolienevandesandt paralleldetectionofsarscov2epitopesrevealsdynamicimmunodominanceprofilesofcd8tmemorycellsinconvalescentcovid19donors |