Memory TCR repertoires analyzed long-term reflect those selected during the primary response

Area of Science:

• Immunology
• T cell biology
• Adaptive immunity

Background:

• Understanding T cell repertoire selection in antigen-specific responses is crucial but limited.
• Previous work identified a specific CD8 T cell expansion (Vbeta10 TCR) in an MHC class I-restricted response.
• This expansion allows direct ex vivo identification of antigen-selected T cells.

Purpose of the Study:

• To investigate the stability and potential evolution of the T cell receptor (TCR) repertoire during antigen-specific immune responses.
• To monitor the usage of a specific TCR alpha chain (Valpha8) in conjunction with the previously identified Vbeta10 TCR.

Main Methods:

• Utilized four-color flow cytometry to analyze TCR Valpha8 expression on antigen-selected Vbeta10(+) CD8 T cells.
• Monitored TCR repertoire stability in individual mice over extended periods (>1 year).
• Assessed the impact of repeated antigenic challenge on repertoire composition.

Main Results:

• Demonstrated significant inter-animal variation in Valpha8 usage within the T cell repertoire.
• Showed that individual mouse repertoires remained remarkably stable over time, irrespective of antigenic challenge.
• Indicated that re-exposure to antigen does not appear to alter the TCR repertoire established during the primary response.

Conclusions:

• The T cell repertoire, particularly in terms of Valpha8 usage on Vbeta10(+) cells, exhibits long-term stability.
• Repeated antigenic stimulation does not significantly skew the established TCR repertoire during this specific immune response.
• The findings suggest that the primary response shapes a stable TCR repertoire that is resilient to subsequent challenges.