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Authors; Annika Nelde, Tatjana Bilich, Jonas S. Heitmann, Yacine Maringer, Helmut R. Salih, Malte Roerden, Maren Lübke, Jens Bauer, Jonas Rieth, Marcel Wacker, Andreas Peter, Sebastian Hörber, Bjoern Traenkle, Philipp D. Kaiser, Ulrich Rothbauer, Matthias Becker, Daniel Junker, Gérard Krause, Monika Strengert, Nicole Schneiderhan-Marra, Markus F. Templin, Thomas O. Joos, Daniel J. Kowalewski, Vlatka Stos-Zweifel, Michael Fehr, Michael Graf, Lena-Christin Gruber, David Rachfalski, Beate Preuß, Ilona Hagelstein, Melanie Märklin, Tamam Bakchoul, Cécile Gouttefangeas, Oliver Kohlbacher, Reinhild Klein, Stefan Stevanović, Hans-Georg Rammensee, Juliane S. Walz 

Journal/ Pre-Print:Research Square 

Tags: Immunology/Immunity, T-cell therapy 

Research Highlights

  1. Characterization of SARS-CoV-2 T-cell epitopes and demonstration of increased responses and recognition rate of T-cell epitopes in convalescent donors compared to unexposed individuals 

  1. Cross-reactive T cell epitopes were identified with similarities to other common cold coronaviruses, suggesting some heterologous immunity 

  1. Some donors with borderline/no IgG responses demonstrated some T cell responses, suggesting that antibody testing may not be sufficient for serosurveillance 


In a well-described methodical analysis, Nelde et al. use the integration of algorithms to identify SARS-CoV-2-derived HLA Class I and II peptides (covering selected HLA-A, B, C and DR haplotypes) from SARS-CoV-2 convalescents and unexposed healthy controls (pre-COVID-19 samples)Characterization of T-cell responses revealed an IFNγ+CD8+ response directed against HLA class I-binding peptides, whereas HLA-DR-binding peptides were recognised by multifunctional (IFNγ+TNF+CD107a+) CD4+ T cells. Similarities between recognised SARS-CoV-2 epitopes and seasonal common cold coronaviruses were identified. Importantly, in a significant percentage of donors with no IgG responses, T cell responses were present, indicating the presence of T cell immunity that may not manifest on antibody testing.  

Impact for SARS-CoV2/COVID19 research efforts  

Desription of SARS-CoV-2 epitopes. 

Study Type  

  • Ex vivo/pre-clinical Study (SARS-CoV-2 convalescents (n=180), unexposed (n=185))  

Strengths and limitations of the paper 

Novelty: Characterization of SARS-CoV-2 T-cell epitopes and evidence for T cell cross-reactivity with other coronaviruses. 

Standing in the field: Expands previous studies with larger dataset.  

Appropriate statistics: YesUnpaired students-t test, Mann-Whitney-U test or Kruskal- Wallis-test with appropriate corrections. 

Viral model used: Clinical samples from convalescent patients. 

Translatability: Deeper understanding of epitopes provided. There is a potential need for detection of multiple epitopes by T cells for protective responses to develop – multiepitope vaccines may therefore be required.   

Main limitations:  

  • Limited phenotype characterization of SARS-CoV-2 responding T cells.  

  • While overall the discovery process covered 97.6% of the world population’s allotype, this was only around 70% for Class II therefore leaving a potential gap in CD4+ understanding.  

  • A matched case control study would be required to determine whether T cells mediate heterologous immunity