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Probing the T-cell receptor repertoire with deep sequencing

Miconnet, Isabelle

Current Opinion in HIV & AIDS: January 2012 - Volume 7 - Issue 1 - p 64–70
doi: 10.1097/COH.0b013e32834ddcae
SYSTEMS BIOLOGY IN UNDERSTANDING HIV PATHOGENESIS AND GUIDING VACCINE DEVELOPMENT: Edited by Rafick-Pierre Sekaly and Bali Pulendran

Purpose of review: To review major findings on the T-cell receptor (TCR) repertoire diversity in response to several viral infections based on conventional methods of PCR, cloning and sequencing and to discuss their limitations in light of the recent methodological advances in deep sequencing.

Recent findings: Direct sequencing of TCR expressed by Ag-specific T cells isolated ex vivo has revealed that the TCR repertoire is not as restricted as previously estimated. Furthermore, analyses performed independently of the T-cell clonal hierarchy have brought to light an unexpected diversity. The choice of methods is critical to characterize the complexity of the repertoire. Recent advances in deep sequencing have uncovered the diversity of the TCR repertoire and shown that the size of the repertoire in naive and Ag-experienced memory T cells is three-fold to 15-fold larger than formerly estimated. Interestingly, the TCR complementary determining region 3 sequences are not randomly selected and a certain degree of shared TCR repertoire has been observed between different individuals.

Summary: Deep sequencing is a major methodological advance allowing more accurate molecular characterization of the TCR repertoire. In the near future, such technologies will further contribute to delineate the complexity of pathogen-specific T-cell response and help defining correlates of a protective immunity.

Division of Immunology and Allergy, Department of Medicine, University Hospital Center, University of Lausanne, Lausanne, Switzerland

Correspondence to Dr Isabelle Miconnet, Division of Immunology and Allergy, University Hospital Center, University of Lausanne, 1011 Lausanne, Switzerland. Tel: +41 21 3141073; fax: +41 21 3140801; e-mail: Isabelle.miconnet@chuv.ch

© 2012 Lippincott Williams & Wilkins, Inc.