TCR repertoire: size, diversity, and function

National Institute On Aging

Investigators

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Abstract

To determine the size and content of alpha/beta TCR repertoires of CD4 and CD8 T cells and their changes with age, we are conducting a longitudinal analysis of alpha/beta TCR repertoires of nave and memory CD4 and CD8 T cells from 30 healthy adults aged from 25 to 85 at first visit and an average of 9-year follow-up as second visit by RNAseq combined with unique molecular identifier technology to reduce errors from PCR and sequencing. To date, we have completed 90% of the sequencing. Our preliminary data from analyzing 1.5 x 108 nave CD4 and CD8 T cells with 1.8 x 109 sequence reads showed that there were 1 x 106 and 4 x 106 unique TCRalpha and TCRbeta, respectively. We found change of nave TCR repertoire size with age was highly individualized. Currently, we are finishing up the remaining sequencing of the project. Recently, we have successfully analyzed CD8+ TCR repertoires against influenza A virus (IAV) M1-GIL peptide at the single cell level. Our objective is to determine whether the profiles (TCR repertoire, phenotype and transcriptome) of IAV M1-specific CD8 T cells can be used to predict the quality of immune response to influenza vaccine in the old population. To test that, we have proposed a study to analyze TCR repertoire, phenotype and transcriptome of selected IAV M1-GIL-specific CD8 T cells in blood prior (0 day) and post (7 and 21 days) vaccination in 50 HLA-A2+ adults age 70 years and older. We will start this study in late fall and winter of 2017.