Rubelt et al. 2016

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Study Description

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 approximately 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.

Link to Publication and ImmPort and to SRA project/samples

Study Contacts

  • Principal Investigator: Mark M. Davis
  • Study Contact: Florian Rubelt, frubelt at stanford dot edu

Study Highlights

  • organism: Human
  • donor status: healthy adults
  • tissue: peripheral blood mononuclear cells
  • cell types:
    • naive B cells: CD20+ CD27-
    • memory B cells: CD20+ CD27+ CD38low
    • naive CD4+ T cells: CD4+ CD8- CD45RO-
    • naive CD8+ T cells: CD8+ CD4- CD45RO-
    • central memory CD4+ T cells: CD4+ CD8- CD45RO+ CCR7+
    • central memory CD8+ T cells: CD8+ CD4- CD45RO+ CCR7+
  • target substrate: mRNA
  • amplification: 5' RACE

Sequence Processing

The resulting sequences were run through IgBlast on the VDJServer platform to generate VDJML and tab-separated values files containing germline alignment information.

Files for Download