Modifications in Immune Response Patterns Induced by Kynurenine and One-Residue-Substituted T Cell Epitopes in SARS-CoV-2-Specific Human T Cells

• Published in: COVID 2024-10, Vol.4 (10), p.1676-1683
• Main Authors: Tokano, Mieko, Takagi, Rie, Matsushita, Sho
• Format: Article
• Language: English
• Subjects: CD4+ T cells; COVID-19; HLA-DR; IL-8; kynurenine
• ISSN: 2673-8112; 2673-8112
• DOI: 10.3390/covid4100116

Peptide p176-190, derived from the SARS-CoV-2 spike protein, is one of the major T cell epitopes that elicits the HLA-DR-restricted IL-8 response of human CD4+ T cells. Using PBMCs from a healthy individual primed with an S-protein-based SARS-CoV-2 vaccine, we established a CD4+ T cell line (TM45) and cloned T cells (TM45.2) specific for the peptide. We showed that (i) co-incubation with kynurenine leads to increased IL-8; (ii) T cells incubated in the absence of kynurenine recovered the original levels of cytokine production; and (iii) peptide p176-190 substituted at 176 Leucine for neutral hydrophilic serine completely abolished the cytokine responses of TM45.2 cells, thereby suggesting that 176 L is the first anchor residue for binding to HLA-DR. These observations collectively indicate that (i) enhanced IL-8 responses can be induced by kynurenine, which is produced under infectious conditions in COVID-19; (ii) the response is not a permanent change in the T cell phenotype; and (iii) IL-8 responses associated with harmful neutrophil extracellular traps can be abrogated by a single amino acid substitution of the viral antigens. These findings may shed light on a novel strategy for designing vaccines for viral infections that are accompanied by increased kynurenine production.