NDLI: A stochastic T cell response criterion

Content Provider	PubMed Central
Author	Currie, James Castro, Mario Lythe, Grant Palmer, Ed Carmen, Molina-parís
Copyright Year	2012
Abstract	The adaptive immune system relies on different cell types to provide fast and coordinated responses, characterized by recognition of pathogenic challenge, extensive cellular proliferation and differentiation, as well as death. T cells are a subset of the adaptive immune cellular pool that recognize immunogenic peptides expressed on the surface of antigen-presenting cells by means of specialized receptors on their membrane. T cell receptor binding to ligand determines T cell responses at different times and locations during the life of a T cell. Current experimental evidence provides support to the following: (i) sufficiently long receptor–ligand engagements are required to initiate the T cell signalling cascade that results in productive signal transduction and (ii) counting devices are at work in T cells to allow signal accumulation, decoding and translation into biological responses. In the light of these results, we explore, with mathematical models, the timescales associated with T cell responses. We consider two different criteria: a stochastic one (the mean time it takes to have had N receptor–ligand complexes bound for at least a dwell time, τ, each) and one based on equilibrium (the time to reach a threshold number N of receptor–ligand complexes). We have applied mathematical models to previous experiments in the context of thymic negative selection and to recent two-dimensional experiments. Our results indicate that the stochastic criterion provides support to the thymic affinity threshold hypothesis, whereas the equilibrium one does not, and agrees with the ligand hierarchy experimentally established for thymic negative selection.
Related Links	http://dx.doi.org/10.1098/rsif.2012.0205
Ending Page	2870
Page Count	15
Starting Page	2856
File Format	PDF
ISSN	17425689
e-ISSN	17425662
Journal	Journal of the Royal Society Interface
Issue Number	76
Volume Number	9
Language	English
Publisher	The Royal Society
Publisher Date	2012-11-07
Access Restriction	Open
Rights Holder	The Royal Society
Subject Keyword	Biotechnology Biophysics Biochemistry Bioengineering Biomaterials Biomedical Engineering Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Biochemistry Biomaterials Biophysics Bioengineering Biomedical Engineering Biotechnology

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1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
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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