TY - JOUR
T1 - Parallel detection of SARS-CoV-2 epitopes reveals dynamic immunodominance profiles of CD8+ T memory cells in convalescent COVID-19 donors
AU - van den Dijssel, Jet
AU - Hagen, Ruth R.
AU - de Jongh, Rivka
AU - Steenhuis, Maurice
AU - Rispens, Theo
AU - Geerdes, Dionne M.
AU - Mok, Juk Yee
AU - Kragten, Angela H. M.
AU - Duurland, Mariël C.
AU - Verstegen, Niels J. M.
AU - van Ham, S. Marieke
AU - van Esch, Wim J. E.
AU - van Gisbergen, Klaas P. JM
AU - Hombrink, Pleun
AU - ten Brinke, Anja
AU - van de Sandt, Carolien E.
N1 - Funding Information: We thank all donors who participated in the study, the Sanquin COVID-19 cryo and biobank facility for processing of samples and the Sanquin Core Facility: Erik Mul, Simon Tol and Mark Hoogenboezem for providing technical assistance. CES has received funding from the European Union's Horizon 2020 research, innovation programme under the Marie Skłodowska-Curie grant agreement (#792532). Funding Information: We thank all donors who participated in the study, the Sanquin COVID‐19 cryo and biobank facility for processing of samples and the Sanquin Core Facility: Erik Mul, Simon Tol and Mark Hoogenboezem for providing technical assistance. CES has received funding from the European Union's Horizon 2020 research, innovation programme under the Marie Skłodowska‐Curie grant agreement (#792532). Publisher Copyright: © 2022 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - CD8 T cells
KW - SARS-CoV-2
KW - convalescence
KW - epitopes
KW - immunodominance
KW - infection
UR - http://www.scopus.com/inward/record.url?scp=85141135759&partnerID=8YFLogxK
UR - https://pure.uva.nl/ws/files/127354173/Supporting_Information_Parallel_detection_of_SARS_CoV_2_epitopes.pdf
U2 - https://doi.org/10.1002/cti2.1423
DO - https://doi.org/10.1002/cti2.1423
M3 - Article
C2 - 36254196
SN - 2050-0068
VL - 11
JO - Clinical & translational immunology
JF - Clinical & translational immunology
IS - 10
M1 - e1423
ER -