Clonal and constricted T cell repertoire in Common Variable Immune Deficiency

Area of Science:

• Immunology
• Genetics

Background:

• Common Variable Immune Deficiency (CVID) is a primary immunodeficiency characterized by hypogammaglobulinemia.
• The T cell receptor (TCR) plays a crucial role in adaptive immunity, and its repertoire diversity is essential for effective immune responses.

Purpose of the Study:

• To investigate the structure and composition of the T cell receptor β chain (TCRβ) in adult patients with CVID.
• To identify potential intrinsic T cell defects contributing to CVID pathogenesis.

Main Methods:

• High-throughput sequencing of TCRβ CDR3 regions from genomic DNA of 44 adult CVID subjects and 22 healthy controls.
• Utilized high-throughput multiplex PCR for amplification and sequencing.

Main Results:

• CVID subjects displayed significantly reduced junctional diversity and fewer n-nucleotide insertions/deletions in TCRβ CDR3 sequences compared to controls.
• A population of highly modified TCRs (≥13 V-gene nucleotide deletions), present in healthy individuals, was absent in CVID patients.
• CVID TCRβ CDR3 sequences were more clonal, exhibited unique V gene usage, and shared fewer sequences with controls, independent of selection.

Conclusions:

• The study provides evidence for an inherent T cell defect in CVID, characterized by abnormalities in TCRβ repertoire structure and composition.
• These TCR abnormalities are pervasive and not associated with specific clinical complications or infectious exposures.