High-throughput sequencing reveals an altered T cell repertoire in X-linked agammaglobulinemia

Manish Ramesh, Noa Simchoni, David Hamm, Charlotte Cunningham-Rundles

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

To examine the T cell receptor structure in the absence of B cells, the TCR β CDR3 was sequenced from DNA of 15 X-linked agammaglobulinemia (XLA) subjects and 18 male controls, using the Illumina HiSeq platform and the ImmunoSEQ analyzer. V gene usage and the V-J combinations, derived from both productive and non-productive sequences, were significantly different between XLA samples and controls. Although the CDR3 length was similar for XLA and control samples, the CDR3 region of the XLA T cell receptor contained significantly fewer deletions and insertions in V, D, and J gene segments, differences intrinsic to the V(D)J recombination process and not due to peripheral T cell selection. XLA CDR3s demonstrated fewer charged amino acid residues, more sharing of CDR3 sequences, and almost completely lacked a population of highly modified Vβ gene segments found in control DNA, suggesting both a skewed and contracted T cell repertoire in XLA.

Original languageEnglish (US)
Article number7544
Pages (from-to)190-196
Number of pages7
JournalClinical Immunology
Volume161
Issue number2
DOIs
StatePublished - Dec 1 2015

Keywords

  • Amino acid sequence
  • High throughput sequencing
  • Junctional diversity
  • T cell receptor
  • XLA

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy

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