Individual heritable differences result in unique cell lymphocyte receptor repertoires of naïve and antigen-experienced cells

Florian Rubelt, Christopher R. Bolen, Helen M. McGuire, Jason A Vander Heiden, Daniel Gadala-Maria, Mikhail Levin, Ghia M. Euskirchen, Murad R. Mamedov, Gary E. Swan, Cornelia L. Dekker, Lindsay G. Cowell, Steven H. Kleinstein, Mark M. Davis

Research output: Contribution to journalArticlepeer-review

53 Scopus citations

Abstract

The adaptive immune systemâ €™ s capability to protect the body requires a highly diverse lymphocyte antigen receptor repertoire. However, the influence of individual genetic and epigenetic differences on these repertoires is not typically measured. By leveraging the unique characteristics of B, CD4+ T and CD8+ T-lymphocyte subsets from monozygotic twins, we quantify the impact of heritable factors on both the V(D)J recombination process and on thymic selection. We show that the resulting biases in both V(D)J usage and N/P addition lengths, which are found in naïve and antigen experienced cells, contribute to significant variation in the CDR3 region. Moreover, we show that the relative usage of V and J gene segments is chromosomally biased, with ∼1.5 times as many rearrangements originating from a single chromosome. These data refine our understanding of the heritable mechanisms affecting the repertoire, and show that biases are evident on a chromosome-wide level.

Original languageEnglish (US)
Article number11112
JournalNature communications
Volume7
DOIs
StatePublished - Mar 23 2016

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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