The LCMV gp33-specific memory T cell repertoire narrows with age

Area of Science:

• Immunology
• T cell receptor repertoire diversity
• Viral immunology

Background:

• CD8+ T cell memory to LCMV persists long-term in mice, conferring resistance to disease.
• While T cell numbers remain stable, TCR diversity is less studied.
• A broad T cell response is generally considered more effective against viral escape.

Purpose of the Study:

• To investigate the TCR usage diversity in CD8+ T cell memory responses to LCMV.
• To determine how TCR diversity changes over time post-infection.
• To assess if TCR diversity differs between high and low tetramer-binding T cells.

Main Methods:

• Analysis of TCRβ sequences in gp33-specific CD8+ T cells at various time points post-LCMV infection.
• Sorting of gp33-specific CD8+ T cells based on tetramer binding affinity.
• Assessment of TCR diversity in NP396-specific CD8+ T cells.

Main Results:

• The primary CD8+ T cell response to LCMV gp33-41 is initially diverse but becomes significantly restricted over time.
• By 26 months post-infection, the response is dominated by a few TCRβ sequences.
• Both high and low tetramer-binding gp33-specific CD8+ T cells showed restricted diversity, dominated by a small number of clones.
• No public clones (shared CDR3 sequences across mice) were identified in the gp33-specific response.

Conclusions:

• LCMV infection leads to a substantial narrowing of the CD8+ T cell receptor repertoire specific for the gp33 epitope.
• This repertoire restriction may underlie the decreased immune response effectiveness observed in aging.
• The findings highlight the importance of TCR diversity in maintaining long-term immune memory efficacy.