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

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.