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The CD8+ T-cell receptor (TCR) repertoire in extremely preterm neonates is highly shared and convergent
Journal article   Peer reviewed

The CD8+ T-cell receptor (TCR) repertoire in extremely preterm neonates is highly shared and convergent

Alison J Carey, Jennifer L Hope, Adam J Fike, Yvonne M Mueller, Linda T Nguyen, Ogan K Kumova, David BH Van Zessen, Mirjam van der Burg and Peter D Katsikis
The Journal of immunology (1950), v 198(1_Supplement), 202.10
01 May 2017
DOI: https://doi.org/10.4049/jimmunol.198.Supp.202.10

Abstract

Neonates have an immunological immaturity which persists from fetal life into the newborn period and can result in a poorly protective response to intracellular pathogens. We have previously shown a less complex TCR repertoire may be responsible for reduced CD8+ T cell immunity in a neonatal murine model of influenza virus infection. Therefore, we sought to determine if there were similar differences in the TCR repertoire across the human life span. High-throughput sequencing of the TCRβ CDR3 regions was performed in sorted, naïve CD8+ T cells from extremely preterm (23–27 weeks gestation), term (39–40 weeks gestation), children aged 16 months to 4 years old, and adults aged 25–50 years (n=5 in each group). There were differences in the CDR3 length across the life span, with preterm infants having a shorter CDR3 length, which was due to fewer N1 and N2 additions (p<0.01) than their term counterparts, which inherently decreases junctional diversity. There was no increase in trimming at the 5′ and 3′ ends of the VDJ genes across the lifespan. Preterm neonates had a striking number of shared clonotypes (8% of total clonotypes) versus their term counterparts (3%) and adults (1%). Convergent recombination describes the phenomenon that identical TCR specificities at the amino acid level can be obtained through different nucleotide sequences. Upon analysis of the most highly shared clones (common to at least 4 samples/age group), the preterm neonate had 12 nucleotide rearrangements per highly shared amino acid sequence, compared to 6 rearrangements at term and 5 in the adult. Our analysis demonstrates the prevalence of shared, convergent clonotypes within the preterm TCR repertoire suggestive of an antigen-driven shaping of the TCR repertoire in utero.

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