Public T cell receptor beta-chains are not advantaged during positive selection.

Area of Science:

• Immunology
• T cell biology
• Molecular immunology

Background:

• Public T cell receptor (TCR) beta-chain rearrangements are observed to dominate antigen-specific and naive T cell repertoires across individuals.
• This suggests potential advantages during T cell development and selection.

Purpose of the Study:

• To investigate the dominance of a specific TCR beta-chain rearrangement (Vbeta8.2-Jbeta2.3) in mouse T cells responding to the HYDbSmcy antigen.
• To determine if public TCR beta-chains are favored during thymic or peripheral selection and consequently over-represented in the naive repertoire.

Main Methods:

• Sequencing of Vbeta8.2-Jbeta2.3 complementarity determining region 3 (CDR3) loops from naive T cell repertoires of multiple mice.
• Analysis of public TCR beta-chain sequences across different repertoires and MHC haplotypes.
• Utilizing bone marrow competition chimeras to track T cell development and assess thymic selection efficiency of individual beta-chains.

Main Results:

• A shared Vbeta8.2-Jbeta2.3 TCR gene rearrangement was identified in mouse T cells responding to the HYDbSmcy antigen.
• Public TCR beta-chain sequences were found across diverse mouse repertoires and MHC haplotypes.
• Thymic positive selection efficiency was similar for beta-chains regardless of their CDR3 loop sequence.

Conclusions:

• The dominance of public TCR beta-chains in the periphery is not primarily due to preferential thymic selection.
• Post-thymic events, rather than thymic selection, predominantly control the establishment and maintenance of public beta-chains in the T cell repertoire.