Berg, Hugo van den, 1968-, Molina-Paris, Carmen and Sewell, Andrew K.. (2011) Specific T-cell activation in an unspecific T-cell repertoire. Science Progress, Vol.94 (No.3). pp. 245-264. ISSN 0036-8504

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Abstract

T-cells are a vital type of white blood cell that circulate around our bodies, scanning for cellular abnormalities and infections. They recognise disease-associated antigens via a surface receptor called the T-cell antigen receptor (TCR). If there were a specific TCR for every single antigen, no mammal could possibly contain all the T-cells it needs. This is clearly absurd and suggests that T-cell recognition must, to the contrary, be highly degenerate. Yet highly promiscuous TCRs would appear to be equally impossible: they are bound to recognise self as well as non-self antigens. We review how contributions from mathematical analysis have helped to resolve the paradox of the promiscuous TCR. Combined experimental and theoretical work shows that TCR degeneracy is essentially dynamical in nature, and that the T-cell can differentially adjust its functional sensitivity to the salient epitope, "tuning up" sensitivity to the antigen associated with disease and "tuning down" sensitivity to antigens associated with healthy conditions. This paradigm of continual modulation affords the TCR repertoire, despite its limited numerical diversity, the flexibility to respond to almost any antigenic challenge while avoiding autoimmunity.

Item Type:	Journal Article
Subjects:	Q Science > QR Microbiology
Divisions:	Faculty of Science > Mathematics
Library of Congress Subject Headings (LCSH):	T cells -- Mathematical models
Journal or Publication Title:	Science Progress
Publisher:	Science Reviews 2000 Ltd.
ISSN:	0036-8504
Date:	September 2011
Volume:	Vol.94
Number:	No.3
Page Range:	pp. 245-264
Identification Number:	10.3184/003685011X13139280383942
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Restricted or Subscription Access
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URI:	http://wrap.warwick.ac.uk/id/eprint/36770

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