Shorter TCR β-Chains Are Highly Enriched During Thymic Selection and Antigen-Driven Selection.

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• The adaptive immune system generates diverse T cell receptors (TCRs) to recognize pathogens.
• The relationship between TCR structure and T cell state heterogeneity is not fully understood.

Purpose of the Study:

• To investigate how T cell receptor (TCR) β-chain complementary-determining region 3 (CDR3) characteristics correlate with T cell states.
• To explore the role of TCR CDR3 length and composition in thymic and antigen-driven selection.

Main Methods:

• Isolation of pure naive and memory CD4+/CD8+ T cells using polychromatic flow cytometry.
• Deep sequencing of TCRβ CDR3 repertoires from isolated T cell populations.

Main Results:

• Shorter TCRβ CDR3s with fewer insertions are enriched during thymic selection.
• Antigen-experienced (memory) T cells exhibit shorter TCRβ CDR3s compared to naive T cells.
• Public TCRβ CDR3 clonotypes are characterized by shorter length and larger size than private clonotypes.

Conclusions:

• Shorter TCRβ CDR3s are consistently enriched during thymic selection, antigen-driven selection, and in public T cell responses.
• Evolutionary pressures may favor shorter CDR3 sequences for recognizing a broad range of antigens.