Monitoring the T-cell receptor repertoire at single-clone resolution

PLoS One. 2006 Dec 20;1(1):e55. doi: 10.1371/journal.pone.0000055.

Abstract

The adaptive immune system recognizes billions of unique antigens using highly variable T-cell receptors. The alphabeta T-cell receptor repertoire includes an estimated 10(6) different rearranged beta chains per individual. This paper describes a novel micro-array based method that monitors the beta chain repertoire with a resolution of a single T-cell clone. These T-arrays are quantitative and detect T-cell clones at a frequency of less than one T cell in a million, which is 2 logs more sensitive than spectratyping (immunoscope), the current standard in repertoire analysis. Using T-arrays we detected CMV-specific CD4+ and CD8+ T-cell clones that expanded early after viral antigen stimulation in vitro and in vivo. This approach will be useful in monitoring individual T-cell clones in diverse experimental settings, and in identification of T-cell clones associated with infectious disease, autoimmune disease and cancer.

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Amino Acid Sequence
  • Antigens, Viral / administration & dosage
  • Antigens, Viral / genetics
  • Base Sequence
  • Clone Cells
  • Cytomegalovirus / genetics
  • Cytomegalovirus / immunology
  • DNA / genetics
  • Gene Rearrangement, beta-Chain T-Cell Antigen Receptor*
  • Humans
  • In Vitro Techniques
  • Jurkat Cells
  • Oligonucleotide Array Sequence Analysis / methods*
  • Receptors, Antigen, T-Cell, alpha-beta / genetics*
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Cytotoxic / cytology
  • T-Lymphocytes, Cytotoxic / immunology

Substances

  • Antigens, Viral
  • Receptors, Antigen, T-Cell, alpha-beta
  • DNA