Trilineage Sequencing Reveals Complex TCRβ Transcriptomes in Neutrophils and Monocytes Alongside T Cells

Area of Science:

• Immunology
• Molecular Biology
• Genomics

Background:

• Recent studies suggest T cell receptor (TCR)-based immune receptors exist beyond T cells, specifically in neutrophils and monocytes/macrophages.
• The complexity and diversity of these receptors in non-T cells remain largely unexplored.

Purpose of the Study:

• To investigate the presence and complexity of T cell receptor beta (TCRβ) transcriptomes in human circulating monocytes and neutrophils.
• To compare the TCRβ repertoires of neutrophils, monocytes, and T cells within individuals and across different individuals.
• To explore the impact of monocyte differentiation into macrophages on immune repertoire diversity.

Main Methods:

• Utilized a semiquantitative trilineage immune repertoire sequencing approach.
• Applied rigorous bioinformatic analyses to assess TCRβ transcriptomes.
• Conducted intraindividual and interindividual comparative analyses of leukocyte TCRβ repertoires.

Main Results:

• Identified highly complex TCRβ transcriptomes in human monocytes and neutrophils, with repertoire diversities significantly smaller than T cells.
• Demonstrated distinct TCRβ repertoires across neutrophils, monocytes, and T cells, with minimal (<0.1%) repertoire sharing.
• Observed that the majority of expressed TCRβ variants are private (individual-specific) across all three leukocyte types.
• Revealed substantial individual-specific repertoire shifts during monocyte-to-macrophage differentiation.

Conclusions:

• Uncovered significant complexity in the TCRβ repertoires of neutrophils and monocytes, suggesting functional immune roles.
• Highlighted the distinct and largely private nature of TCRβ repertoires in these phagocytes compared to T cells.
• Demonstrated remarkable immune repertoire plasticity in the monocyte lineage during differentiation, challenging previous assumptions.