Functionally specialized human CD4⁺ T-cell subsets express physicochemically distinct TCRs

Area of Science:

• Immunology
• Molecular Biology

Background:

• Adaptive immunity relies on distinct CD4+ T cell subsets.
• The influence of T-cell receptors (TCRs) on CD4+ T cell lineage choice remains incompletely understood.

Purpose of the Study:

• To investigate how clonotypically expressed TCRs shape CD4+ T cell subset differentiation.
• To profile TCR repertoires across human naive and effector/memory CD4+ T cell subsets.

Main Methods:

• High-throughput sequencing of αβ TCR repertoires.
• Analysis of physicochemical and recombinatorial TCR features.
• Clonal tracking to map T cell subset interconversions.

Main Results:

• Subset-specific conserved features were identified in effector/memory CD4+ T cells.
• Distinct transition pathways between T cell subsets were mapped.
• Public TCR sequences and hardwired naive repertoire features were observed in regulatory T cells (Tregs).

Conclusions:

• Intrinsic TCR properties significantly influence CD4+ T cell fate decisions.
• Repertoire portraits reveal links between clonotype behavior and TCR characteristics.
• TCRs play a crucial role in maintaining the organizational integrity of the adaptive immune system.