Signal integration in thymocytes is crucial for thymic selection

Abstract

Event Abstract Back to Event Signal integration in thymocytes is crucial for thymic selection Sahamoddin Khailaie1, Aras Toker2, Jochen Huehn2 and Michael Meyer-Hermann1, 3* 1 Department of Systems Immunology, Helmholtz Center for Infection Research, Germany 2 Department of Experimental Immunology, Helmholtz Center for Infection Research, Germany 3 Bio Center for Life Science, Technische Universität Braunschweig, Germany Thymocytes are generated, selected and mature in the thymus to create a diverse, functional and self-tolerant T cell repertoire. Selection of thymocytes relies on the level of their T cell receptor (TCR) self-reactivity. Self-reactivity of thymocytes is quantified by repeated engagement of their TCRs with a diverse repertoire of self-peptides complexed with self-MHC molecule (spMHC) and may originate from either part of the complex. The role and relative importance of MHC versus self-peptides in thymic selection is not resolved. The fact that the selected T cell repertoire is MHC-restricted, requires a good mechanistic explanation of how thymocytes are able to quantify their affinity to MHC. In order to analyze how thymocytes quantify their self-reactivity, extract their MHC affinity, and how they use this information for cell fate determination, we developed a signal integration model for thymic selection, mimicking the requirement of repeated TCR signaling for successful selection and cell maturation. In this model, a polyclonal repertoire of thymocytes sequentially interact with diverse spMHCs and integrate the affinity-dependent TCR ligation signals. The strength and dynamics of the integrated signal is taken as a reference for cell fate determination. Quantification of the integrated signal and discrimination between its sustained and transient dynamics turns out as a successful basis for extracting affinity of thymocytes to MHC, detecting the existence of cognate self-peptide, and selecting a MHC-restricted self-tolerant T cell repertoire. Regulatory T-cell differentiation versus clonal deletion of autoreactive thymocytes is discussed with this model. Keywords: Thymic selection, T cell signaling, MHC restriction, Clonal Deletion, Regulatory T cell differentiation Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Adaptive Immunity Citation: Khailaie S, Toker A, Huehn J and Meyer-Hermann M (2013). Signal integration in thymocytes is crucial for thymic selection. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00479 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 31 Mar 2013; Published Online: 22 Aug 2013. * Correspondence: Prof. Michael Meyer-Hermann, Department of Systems Immunology, Helmholtz Center for Infection Research, Braunschweig, Germany, mmh@theoretical-biology.de Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Sahamoddin Khailaie Aras Toker Jochen Huehn Michael Meyer-Hermann Google Sahamoddin Khailaie Aras Toker Jochen Huehn Michael Meyer-Hermann Google Scholar Sahamoddin Khailaie Aras Toker Jochen Huehn Michael Meyer-Hermann PubMed Sahamoddin Khailaie Aras Toker Jochen Huehn Michael Meyer-Hermann Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.