Identification of cytotoxic T cells and their T cell receptor sequences targeting COVID-19 using MHC class I-binding...

Area of Science:

• Immunology
• Virology
• Molecular Biology

Background:

• Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants pose global health challenges due to increased infectivity and immune evasion.
• Understanding T cell responses is crucial for developing effective vaccines and therapeutics against SARS-CoV-2 and future coronavirus threats.

Purpose of the Study:

• To identify SARS-CoV-2-derived peptide epitopes that can induce CD8+ T cell immunity.
• To investigate the potential of these peptides in eliciting cross-protective T cell responses against various coronaviruses.

Main Methods:

• In silico analysis to predict SARS-CoV-2 peptides binding to human leukocyte antigen (HLA) class I molecules (HLA-A*24:02, HLA-A*02:01, HLA-A*02:06).
• Detection of CD8+ T cells recognizing identified peptides in peripheral blood samples from recovered and non-infected individuals.
• Sequencing of T cell receptor (TCR) pairs from identified cytotoxic T lymphocyte (CTL) clones.

Main Results:

• Fifteen SARS-CoV-2 peptides were identified that bind to specific HLA class I alleles and potentially induce cytotoxic T lymphocytes (CTLs).
• Thirteen peptides originated from ORF1ab polyprotein, one from spike protein, and one from membrane glycoprotein.
• Recognizing CD8+ T cells were found in both COVID-19 survivors and uninfected individuals, suggesting pre-existing or cross-reactive immunity.
• Nine CTL clones with defined TCR sequences recognizing SARS-CoV-2 peptides were characterized.

Conclusions:

• Identified SARS-CoV-2 peptides can induce CD8+ T cell responses, offering potential for therapeutic strategies.
• The conservation of these peptides across multiple coronaviruses suggests their utility in maintaining T cell immunity against current and future pandemic threats.
• Defined TCR sequences may serve as valuable tools for investigating SARS-CoV-2 infection history.