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Trends Immunol. 2014 Dec;35(12):581-590. doi: 10.1016/ Epub 2014 Oct 8.

Characterizing immune repertoires by high throughput sequencing: strategies and applications.

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The Rockefeller University, New York, NY, USA.
The Rockefeller University, New York, NY, USA; John C. Whitehead Presidential Fellows Program, The Rockefeller University, New York, NY, USA. Electronic address:


As the key cellular effectors of adaptive immunity, T and B lymphocytes utilize specialized receptors to recognize, respond to, and neutralize a diverse array of extrinsic threats. These receptors (immunoglobulins in B lymphocytes, T cell receptors in T lymphocytes) are incredibly variable, the products of specialized genetic diversification mechanisms that generate complex lymphocyte repertoires with extensive collections of antigen specificities. Recent advances in high throughput sequencing (HTS) technologies have transformed our ability to examine antigen receptor repertoires at single nucleotide, and more recently, single cell, resolution. Here we review current approaches to examining antigen receptor repertoires by HTS, and discuss inherent biological and technical challenges. We further describe emerging applications of this powerful methodology for exploring the adaptive immune system.


T cell receptor diversity; antibody diversity; high throughput sequencing; immune profiling; immune repertoires; immunoglobulin diversity

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