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Dynamic Tuning of T Cell Receptor Specificity by Co-Receptors and Costimulation

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Mathematical Models and Immune Cell Biology

Abstract

Mounting evidence that each clonotype of T cell antigen receptor can productively interact with hundreds or even thousands of peptide antigens would appear to conflict, prima facie, with the immune system’s primary task of guarding against auto-immunity and singling out harmful “non-self” epitopes against a background of “self” epitopes. This paradox dissolves somewhat once it is appreciated that, at any one time, a TCR will only have high functional sensitivity to a small subset of all its potential agonists, that is, when presented at low copy numbers, only this small subset will be able to activate the T cell. In this light, the self-nonself problem becomes a matter of keeping the TCR trained on the appropriate subset of salient epitopes. We review evidence and models that show how the co-receptors CD4 and CD8, as well as the “signal 2” costimulatory system, act to keep the TCR focussed on the appropriate agonist subset. On the theory of dynamic tuning of TCR specificity, both immune tolerance and specific reactivity against salient epitopes rely on continual regulation by other components of the immune system. We present a model of “avidity maturation” during the early phase of a T cell response.

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Authors and Affiliations

  1. Warwick Systems Biology Centre, University of Warwick, Coventry, CV47AL, UK

    Hugo A. van den Berg

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  1. Hugo A. van den Berg
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  2. Andrew K. Sewell
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Correspondence to Hugo A. van den Berg .

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  1. School of Mathematics, Dept. Applied Mathematics, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, United Kingdom

    Carmen Molina-París

  2. School of Mathematics, Dept. Applied Mathematics, University of Leeds, Woodhouse Lane, Leeds, LS2 9JT, United Kingdom

    Grant Lythe

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van den Berg, H.A., Sewell, A.K. (2011). Dynamic Tuning of T Cell Receptor Specificity by Co-Receptors and Costimulation. In: Molina-París, C., Lythe, G. (eds) Mathematical Models and Immune Cell Biology. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-7725-0_3

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