Parallel detection of SARS-CoV-2 epitopes reveals dynamic immunodominance profiles of CD8+ T memory cells in convalescent COVID-19 donors.
Clin Transl Immunology
; 11(10): e1423, 2022.
Article
in English
| MEDLINE | ID: covidwho-2127656
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*0101/ORF1ab1637-1646 and B*0702/N105-113 and identified B*3501/N325-333 as a third epitope with immunodominant features. The magnitude of subdominant epitope responses, including A*0301/N361-369 and A*0201/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.
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Type of study:
Prognostic study
/
Randomized controlled trials
Topics:
Vaccines
Language:
English
Journal:
Clin Transl Immunology
Year:
2022
Document Type:
Article
Similar
MEDLINE
...
LILACS
LIS