title: Sequence analysis of T-cell repertoires in health and disease.
abstract: T-cell antigen receptor (TCR) variability enables the cellular immune system to discriminate between self and non-self. High-throughput TCR sequencing (TCR-seq) involves the use of next generation sequencing platforms to generate large numbers of short DNA sequences covering key regions of the TCR coding sequence, which enables quantification of T-cell diversity at unprecedented resolution. TCR-seq studies have provided new insights into the healthy human T-cell repertoire, such as revised estimates of repertoire size and the understanding that TCR specificities are shared among individuals more frequently than previously anticipated. In the context of disease, TCR-seq has been instrumental in characterizing the recovery of the immune repertoire after hematopoietic stem cell transplantation, and the method has been used to develop biomarkers and diagnostics for various infectious and neoplastic diseases. However, T-cell repertoire sequencing is still in its infancy. It is expected that maturation of the field will involve the introduction of improved, standardized tools for data handling, deposition and statistical analysis, as well as the emergence of new and equivalently large-scale technologies for T-cell functional analysis and antigen discovery. In this review, we introduce this nascent field and TCR-seq methodology, we discuss recent insights into healthy and diseased TCR repertoires, and we examine the applications and challenges for TCR-seq in the clinic.
authors.affiliation: BC Cancer Agency, Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada ; Genome Sciences & Technology Program, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Woodsworth
authors.affiliation: BC Cancer Agency, Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada ; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
authors.forename: Mauro
authors.initials: M
authors.lastname: Castellarin
authors.affiliation: BC Cancer Agency, Michael Smith Genome Sciences Centre, Vancouver, British Columbia V5Z 1L3, Canada ; Genome Sciences & Technology Program, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada ; Department of Molecular Biology and Biochemistry, Simon Fraser University, Burnaby, British Columbia V5A 1S6, Canada.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Holt