Selection influences naive CD8+ TCR-β repertoire sharing

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• The adaptive immune system generates a vast T-cell receptor (TCR) repertoire to recognize diverse pathogens.
• Theoretical TCR diversity far exceeds the number of T cells, making identical TCRs in different individuals improbable.
• Despite low probability, 'public' TCR sequences are observed in various immune contexts, but their abundance is not fully explained by generation biases.

Purpose of the Study:

• To investigate the distribution of genomic TCR-beta (TCR-β) sequences in naive CD8+ T cells.
• To compare the abundances of productive and non-productive TCR-β sequences.
• To determine the role of selection versus neutral processes in shaping public TCR-β sequence abundance.

Main Methods:

• Analysis of genomic TCR-β sequences from naive CD8+ T cells of three genetically identical mice.
• Comparison of sequence distributions between productive (functional) and non-productive (non-functional) TCR-β repertoires.
• Evaluation of neutral processes (recombination biases, codon degeneracy, generation probability) and selection (thymic or peripheral).

Main Results:

• Public TCR-β sequences were found at higher abundances than unshared sequences in the productive repertoire.
• This abundance difference was not observed in the non-productive repertoire.
• Neutral processes alone could not fully account for the observed higher abundances of public TCR-β sequences.

Conclusions:

• The findings indicate that selection processes play a significant role in increasing the abundance of public TCR-β sequences.
• Both thymic and peripheral selection are implicated in shaping the TCR repertoire.
• Understanding these selection mechanisms is crucial for comprehending immune responses to pathogens, autoimmunity, and cancer.