Defining the alloreactive T cell repertoire using high-throughput sequencing of mixed lymphocyte reaction culture

Ryan O. Emerson*, James M. Mathew, Iwona M. Konieczna, Harlan S. Robins, Joseph R. Leventhal

*Corresponding author for this work

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

The cellular immune response is the most important mediator of allograft rejection and is a major barrier to transplant tolerance. Delineation of the depth and breadth of the alloreactive T cell repertoire and subsequent application of the technology to the clinic may improve patient outcomes. As a first step toward this, we have used MLR and high-throughput sequencing to characterize the alloreactive T cell repertoire in healthy adults at baseline and 3 months later. Our results demonstrate that thousands of T cell clones proliferate in MLR, and that the alloreactive repertoire is dominated by relatively high-abundance T cell clones. This clonal make up is consistently reproducible across replicates and across a span of three months. These results indicate that our technology is sensitive and that the alloreactive TCR repertoire is broad and stable over time. We anticipate that application of this approach to track donor-reactive clones may positively impact clinical management of transplant patients.

Original languageEnglish (US)
Article numbere111943
JournalPloS one
Volume9
Issue number11
DOIs
StatePublished - Nov 3 2014

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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