Two compensatory pathways maintain long-term stability and diversity in CD8 T cell memory repertoires

Area of Science:

• Immunology
• T cell biology
• Human memory T cell repertoires

Background:

• Human memory T cell repertoires are crucial for adaptive immunity but their long-term dynamics are poorly understood.
• Previous work established that influenza M1(58-66) epitope recall responses in HLA-A2 individuals are polyclonal and dominated by BV19 chains with Arg-Ser (RS) in the CDR3 loop.

Purpose of the Study:

• To investigate the longitudinal stability and changes in human memory T cell repertoires over extended periods (7-10 years).
• To analyze the dynamics of specific Arg-Ser (RS) clonotypes within the T cell memory repertoire.

Main Methods:

• Longitudinal analysis of memory T cell repertoires in three middle-aged individuals over 7-10 years.
• Characterization of repertoire stability using metrics like singletons (clonotypes observed once) and clonotypic diversity.
• Focus on the subset of clonotypes utilizing Arg-Ser (RS) in the CDR3 loop.

Main Results:

• A substantial fraction of memory T cell clonotypes remained stable over the 7-10 year observation period.
• Overall repertoire shape, including singleton fraction and diversity, was stable.
• The Arg-Ser (RS) clonotype subset exhibited a significant decline in singleton fraction and clonotypic diversity.

Conclusions:

• Memory T cell repertoire structure is maintained by recruiting new non-RS clonotypes and increasing the frequency of existing RS clonotypes.
• The recruitment of new clonotypes into the low-frequency repertoire suggests their potential functional importance.
• These findings provide insights into the long-term maintenance and plasticity of human adaptive immunity.