Thymic selection defines multiple T cell receptor V beta 'repertoire phenotypes' at the CD4/CD8 subset level

Area of Science:

• Immunology
• Genetics
• Molecular Biology

Background:

• T-cell receptor (TCR) V beta gene expression is crucial for adaptive immunity.
• Understanding TCR repertoire selection is key to deciphering immune responses and disease susceptibility.

Purpose of the Study:

• To characterize the expression levels of 17 V beta genes in CD4+ and CD8+ T cell subsets across different mouse strains.
• To investigate the influence of MHC and non-MHC genes on V beta repertoire selection.
• To explore the relationship between TCR repertoire polymorphisms and disease phenotypes.

Main Methods:

• Utilized a sensitive multiprobe V beta Ribonuclease (RNase) protection assay.
• Analyzed gene expression in separated CD4+ and CD8+ T cell subsets from selected mouse strains.
• Examined TCR V beta repertoire diversity in MHC-identical strains.

Main Results:

• Identified skewed subset expression patterns for IE-reactive V beta genes (V beta 11, 12, 5.1, 16) across mouse strains.
• Observed subset-biased V beta clonal deletions, particularly for V beta 11 and V beta 12 in CD4+ cells.
• Revealed strain- and subset-specific V beta gene expression biases (e.g., V beta 7, 13 in CD8+; V beta 15 in CD4+).
• Demonstrated unique V beta repertoires in MHC-identical strains, highlighting non-MHC ligand influence.

Conclusions:

• TCR V beta repertoire selection is influenced by a combination of MHC and non-MHC genes, as well as T cell subset.
• Negative selection can lead to incomplete and subset-biased V beta clonal deletions.
• Polymorphisms in TCR repertoire expression may serve as markers for disease susceptibility phenotypes.