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 and Mark M. Davis ()
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Florian Rubelt: Stanford University School of Medicine
Christopher R. Bolen: Stanford University School of Medicine
Helen M. McGuire: Stanford University School of Medicine
Jason A. Vander Heiden: Deaptment of Computational Biology & Bioinformatics, Yale University
Daniel Gadala-Maria: Deaptment of Computational Biology & Bioinformatics, Yale University
Mikhail Levin: University of Texas Southwestern Medical Center
Ghia M. Euskirchen: Stanford University School of Medicine
Murad R. Mamedov: Program in Immunology, Stanford University
Gary E. Swan: Stanford Prevention Research Center, Stanford University School of Medicine
Cornelia L. Dekker: Stanford University School of Medicine
Lindsay G. Cowell: University of Texas Southwestern Medical Center
Steven H. Kleinstein: Deaptment of Computational Biology & Bioinformatics, Yale University
Mark M. Davis: Stanford University School of Medicine

Nature Communications, 2016, vol. 7, issue 1, 1-12

Abstract: Abstract The adaptive immune system’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.

Date: 2016
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DOI: 10.1038/ncomms11112

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