NDLI: Activation-threshold tuning in an affinity model for the T-cell repertoire.

Content Provider	PubMed Central
Author	Scherer, Almut André, Noest Boer, Rob J. De
Abstract	Naive T cells respond to peptides from foreign proteins and remain tolerant to self peptides from endogenous proteins. It has been suggested that self tolerance comes about by a 'tuning' mechanism, i.e. by increasing the T-cell activation threshold upon interaction with self peptides. Here, we explore how such an adaptive mechanism of T-cell tolerance would influence the reactivity of the T-cell repertoire to foreign peptides. We develop a computer simulation model in which T cells are tolerized by increasing their activation-threshold dependent on the affinity with which they see self peptides presented in the thymus. Thus, different T cells acquire different activation thresholds (i.e. different cross-reactivities). In previous mathematical models, T-cell tolerance was deletional and based on a fixed cross-reactivity parameter, which was assumed to have evolved to an optimal value. Comparing these two different tolerance-induction mechanisms, we found that the tuning model performs somewhat better than an optimized deletion model in terms of the reactivity to foreign antigens. Thus, evolutionary optimization of clonal cross-reactivity is not required. A straightforward extension of the tuning model is to delete T-cell clones that obtain a too high activation threshold, and to replace these by new clones. The reactivity of the immune repertoires of such a replacement model is enchanced compared with the basic tuning model. These results demonstrate that activation-threshold tuning is a functional mechanism for self tolerance induction.
Related Links	http://dx.doi.org/10.1098/rspb.2003.2653
Ending Page	616
Page Count	8
Starting Page	609
File Format	PDF
ISSN	09628452
e-ISSN	14712954
Journal	Proceedings of the Royal Society B: Biological Sciences
Issue Number	1539
Volume Number	271
Language	English
Publisher Date	2004-03-22
Access Restriction	Open
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Immunology and Microbiology(all) Agricultural and Biological Sciences(all) Environmental Science(all) Medicine(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Immunology and Microbiology Medicine Biochemistry, Genetics and Molecular Biology Environmental Science Agricultural and Biological Sciences

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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