High throughput analysis of natural regulatory and conventional T cell receptor repertoires following human H1N1 vaccination

Due to the vast diversity of the T cell receptor repertoire, it has remained a considerable challenge when investigating whether the “host’s choice” of TCR during infection is related to the immune response and disease outcome. Here we report profiling of the TR repertoire following H1N1 vaccination using 5’RACE, 454 sequencing and IMGT/HighV-QUEST, a novel approach designed to amplify and interpret full length human TR V-BETA transcripts in an unbiased manner. Using this technique, we observed striking bias in TCR gene usage and junction modifications across multiple T cell subsets as well as corresponding bias in unproductive TR sequences, indicating the presence of intrinsic predictability during the human V-(D)-J recombination. CDR3 nucleotide divergence was augmented following vaccination, suggesting an intriguing role for CDR3 in the functional fitness of the TR/pMHC complex. In addition, we provide evidence that the Treg and conventional CD4 T cell repertoires are principally distinct but both mobilized (although with different kinetics) following vaccination.