Abstract
The creation and evolution of the T cell receptor repertoire within an individual combines stochastic and deterministic processes. We systematically examine the structure of the repertoire in different T cell subsets in young, adult and LCMV infected mice, from the perspective of variable gene usage, nucleotide sequences and amino acid motifs. Young individuals share a high level of organization, especially in the frequency distribution of variable genes and amino acid motifs. In adult mice, this structure relaxes and is replaced by idiotypic evolution of the effector and regulatory repertoire. The repertoire of CD4+ regulatory T cells was more similar to naïve cells in young mice, but became more similar to effectors with age. Finally, we observed a dramatic restructuring of the repertoire following infection with LCMV. We hypothesize that the stochastic process of recombination and thymic selection initially impose a strong structure to the repertoire, which gradually relaxes following asynchronous responses to different antigens during life.
Competing Interest Statement
The authors have declared no competing interest.
List of Abbreviations
- TCR
- T cell receptor
- TCR-seq
- High-throughput sequencing of TCR.
- BM
- Bonne-marrow
- SP
- Spleen
- MHC
- Major histocompatibility complex
- CDR3
- Complementarity determining region three
- CDR3NT/CDR3AA
- Nucleotide and amino acid sequences of the CDR3
- UMI
- Unique molecular identifier
- CM
- Central memory T cells
- N
- Naïve T cells
- Treg
- Regulatory T cells
- RT
- Reverse transcription
- cDNA
- Complementary DNA
- V, D and J
- Variable (V), diversity (D) and joining (J) TCR gene segments
- CDR3ntVJ
- CDR3NT sequences with V and J gene segments
- LCMV
- Lymphocytic choriomeningitis virus