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Specific T-cell activation in an unspecific T-cell repertoire
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Berg, Hugo van den , 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. doi:10.3184/003685011X13139280383942 ISSN 0036-8504.
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WRAP_Van_den_berg_150811-theoreticaltcellimmunology.pdf - Accepted Version Download (815Kb) | Preview |
Official URL: http://dx.doi.org/10.3184/003685011X13139280383942
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 | ||||
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Subjects: | Q Science > QR Microbiology | ||||
Divisions: | Faculty of Science, Engineering and Medicine > 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 | ||||
Official Date: | September 2011 | ||||
Dates: |
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Volume: | Vol.94 | ||||
Number: | No.3 | ||||
Page Range: | pp. 245-264 | ||||
DOI: | 10.3184/003685011X13139280383942 | ||||
Status: | Peer Reviewed | ||||
Publication Status: | Published | ||||
Access rights to Published version: | Restricted or Subscription Access | ||||
Date of first compliant deposit: | 17 December 2015 | ||||
Date of first compliant Open Access: | 17 December 2015 |
Data sourced from Thomson Reuters' Web of Knowledge
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