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Clonal Deletion versus Clonal Diversion: Footprints of Self-Tolerance in the T CellRepertoire

Total Cost €


EC-Contrib. €






 TOLERANCE FOOTPRINT project word cloud

Explore the words cloud of the TOLERANCE FOOTPRINT project. It provides you a very rough idea of what is the project "TOLERANCE FOOTPRINT" about.

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Project "TOLERANCE FOOTPRINT" data sheet

The following table provides information about the project.


Organization address
postcode: 80539

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Total cost 2˙414˙500 €
 EC max contribution 2˙414˙500 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-ADG
 Funding Scheme ERC-ADG
 Starting year 2017
 Duration (year-month-day) from 2017-10-01   to  2022-09-30


Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 


 Project objective

Self-tolerance is a key feature of the immune system; its failure causes autoimmune diseases such as Multiple Sclerosis or Type-1-Diabetes. Remarkably, T cell tolerance operates via two fundamentally different mechanisms: potentially dangerous cells are either eliminated (clonal deletion) or re-programmed to differentiate into regulatory T (Treg) cells (clonal diversion). Paradoxically, both tolerance modes can ensue from self-antigen-encounter in the thymus, and the parameters specifying these opposing cell-fates remain poorly understood. Moreover, the relative contribution of clonal deletion versus clonal diversion to tolerance at the level of diverse immune cell repertoires has not been determined. In particular, the paucity of antigen-specific cells is a major experimental obstacle to unravelling to what extent cells with shared autoreactive specificity, yet different T cell receptors (TCRs), are subject to either mode of tolerance. Breakthroughs in visualizing minute cohorts of antigen-specific cells, characterizing the TCRs on individual cells and large-scale TCR sequencing now provide a unique opportunity to tackle these challenging questions. Based upon my expertise in thymus biology and T cell selection, I will exploit these technological advances to reveal where and how tolerance either generates ‘holes’ in the repertoire or diverts cells into a ‘benign’ sub-repertoire. The main objectives are (i) to identify and classify deleted or diverted TCR-entities through comparing ‘uncensored’ and ‘censored’ repertoires in the absence or presence of a disease-relevant autoantigen and (ii) to identify TCR intrinsic features as well as T cell extrinsic determinants that specify clonal deletion versus clonal diversion. The proposed research elucidates a fundamental aspect of vertebrate immunology, but also has major implications regarding the therapeutic promise of harnessing endogenous, antigen-specific Treg cells in autoimmunity.


year authors and title journal last update
List of publications.
2019 Ludger Klein, Ellen A. Robey, Chyi-Song Hsieh
Central CD4+ T cell tolerance: deletion versus regulatory T cell differentiation
published pages: 7-18, ISSN: 1474-1733, DOI: 10.1038/s41577-018-0083-6
Nature Reviews Immunology 19/1 2019-06-07

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