Vaccination-induced T cell responses maintain polyclonality with high antigen receptor avidity

Area of Science:

• Immunology
• Virology
• Genomics

Background:

• Adaptive immunity relies on clonal expansion of T cells.
• Studying human T cell responses is complex compared to animal models.
• Understanding T cell repertoire dynamics is crucial for vaccine development.

Purpose of the Study:

• To characterize CD8 T cell responses in humans after mRNA SARS-CoV-2 vaccination and breakthrough infection.
• To investigate the relationship between T cell receptor (TCR) avidity, clonal expansion, and epitope specificity.
• To explore how T cell repertoire polyclonality contributes to immunity against viral escape variants.

Main Methods:

• ELISpot and flow cytometry to assess T cell responses.
• Single-cell RNA, protein, and TCR sequencing for detailed characterization.
• Reexpression and functional testing of identified TCRs.

Main Results:

• Vaccination-induced T cell repertoires showed enrichment for high-avidity TCRs.
• Differential clonal expansion was not solely driven by minor avidity differences.
• Polyclonality of T cell repertoires was key for combating viral mutational escape.

Conclusions:

• Human T cell repertoire polyclonality enhances robustness against viral escape.
• Deciphering T cell functionality provides insights into human T cell biology.
• Findings may inform the development of improved vaccines and immunotherapies.