T cell and antibody kinetics delineate SARS-CoV-2 peptides mediating long-term immune responses in COVID-19 convalescent individuals

Sci Transl Med. 2021 Apr 21;13(590):eabf7517. doi: 10.1126/scitranslmed.abf7517. Epub 2021 Mar 15.


Long-term immunological memory to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is crucial for the development of population-level immunity, which is the aim of vaccination approaches. Reports on rapidly decreasing antibody titers have led to questions regarding the efficacy of humoral immunity alone. The relevance of T cell memory after coronavirus disease 2019 (COVID-19) remains unclear. Here, we investigated SARS-CoV-2 antibody and T cell responses in matched samples of COVID-19 convalescent individuals up to 6 months after infection. Longitudinal analysis revealed decreasing and stable spike- and nucleocapsid-specific antibody responses, respectively. In contrast, functional T cell responses remained robust, and even increased, in both frequency and intensity. Single peptide mapping of T cell diversity over time identified open reading frame-independent, dominant T cell epitopes mediating long-term SARS-CoV-2 T cell responses. Identification of these epitopes may be fundamental for COVID-19 vaccine design.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Viral / blood
  • Antibodies, Viral / immunology
  • COVID-19 / immunology*
  • Convalescence
  • Coronavirus Nucleocapsid Proteins / immunology
  • Epitopes, T-Lymphocyte / immunology
  • Humans
  • Immunodominant Epitopes / immunology
  • Immunologic Memory*
  • Kinetics
  • Peptide Mapping
  • Phosphoproteins / immunology
  • SARS-CoV-2 / immunology*
  • Spike Glycoprotein, Coronavirus / immunology
  • T-Lymphocytes / immunology*


  • Antibodies, Viral
  • Coronavirus Nucleocapsid Proteins
  • Epitopes, T-Lymphocyte
  • Immunodominant Epitopes
  • Phosphoproteins
  • Spike Glycoprotein, Coronavirus
  • nucleocapsid phosphoprotein, SARS-CoV-2
  • spike protein, SARS-CoV-2