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Human CD4 + T cells specific for dominant epitopes of SARS-CoV-2 Spike and Nucleocapsid proteins with therapeutic potential.
- Source :
-
Clinical and experimental immunology [Clin Exp Immunol] 2021 Sep; Vol. 205 (3), pp. 363-378. Date of Electronic Publication: 2021 Jun 29. - Publication Year :
- 2021
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Abstract
- Since December 2019, Coronavirus disease-19 (COVID-19) has spread rapidly throughout the world, leading to a global effort to develop vaccines and treatments. Despite extensive progress, there remains a need for treatments to bolster the immune responses in infected immunocompromised individuals, such as cancer patients who recently underwent a haematopoietic stem cell transplantation. Immunological protection against COVID-19 is mediated by both short-lived neutralizing antibodies and long-lasting virus-reactive T cells. Therefore, we propose that T cell therapy may augment efficacy of current treatments. For the greatest efficacy with minimal adverse effects, it is important that any cellular therapy is designed to be as specific and directed as possible. Here, we identify T cells from COVID-19 patients with a potentially protective response to two major antigens of the SARS-CoV-2 virus, Spike and Nucleocapsid protein. By generating clones of highly virus-reactive CD4 <superscript>+</superscript> T cells, we were able to confirm a set of nine immunodominant epitopes and characterize T cell responses against these. Accordingly, the sensitivity of T cell clones for their specific epitope, as well as the extent and focus of their cytokine response was examined. Moreover, using an advanced T cell receptor (TCR) sequencing approach, we determined the paired TCR-αβ sequences of clones of interest. While these data on a limited population require further expansion for universal application, the results presented here form a crucial first step towards TCR-transgenic CD4 <superscript>+</superscript> T cell therapy of COVID-19.<br /> (© 2021 The Authors. Clinical & Experimental Immunology published by John Wiley & Sons Ltd on behalf of British Society for Immunology.)
- Subjects :
- Adult
Aged
Aged, 80 and over
Amino Acid Sequence
CD8-Positive T-Lymphocytes immunology
CD8-Positive T-Lymphocytes virology
COVID-19 virology
Clone Cells immunology
Clone Cells virology
Coronavirus Nucleocapsid Proteins chemistry
Coronavirus Nucleocapsid Proteins genetics
Cytokines biosynthesis
Epitopes, T-Lymphocyte chemistry
Epitopes, T-Lymphocyte genetics
Epitopes, T-Lymphocyte immunology
Female
Humans
Immunization, Passive
Immunodominant Epitopes chemistry
Immunodominant Epitopes genetics
Immunodominant Epitopes immunology
Male
Middle Aged
Phosphoproteins chemistry
Phosphoproteins genetics
Phosphoproteins immunology
Receptors, Antigen, T-Cell, alpha-beta genetics
Receptors, Antigen, T-Cell, alpha-beta immunology
SARS-CoV-2 chemistry
SARS-CoV-2 genetics
Spike Glycoprotein, Coronavirus chemistry
Spike Glycoprotein, Coronavirus genetics
COVID-19 Serotherapy
CD4-Positive T-Lymphocytes immunology
CD4-Positive T-Lymphocytes virology
COVID-19 immunology
COVID-19 therapy
Coronavirus Nucleocapsid Proteins immunology
SARS-CoV-2 immunology
Spike Glycoprotein, Coronavirus immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1365-2249
- Volume :
- 205
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Clinical and experimental immunology
- Publication Type :
- Academic Journal
- Accession number :
- 34061349
- Full Text :
- https://doi.org/10.1111/cei.13627