Exploring the MHC-peptide matrix of central tolerance in the human thymus

Adamopoulou, Eleni; Tenzer, Stefan; Hillen, Nina; Klug, Paul; Rota, Ioanna A.; Tietz, Silvia; Gebhardt, Madlen; Stevanovic, Stefan; Schild, Hansjörg; Tolosa, Eva; Melms, Arthur; Stoeckle, Christina (2013). Exploring the MHC-peptide matrix of central tolerance in the human thymus. Nature communications, 4(2039), p. 2039. Nature Publishing Group 10.1038/ncomms3039

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Ever since it was discovered that central tolerance to self is imposed on developing T cells in the thymus through their interaction with self-peptide major histocompatibility complexes on thymic antigen-presenting cells, immunologists have speculated about the nature of these peptides, particularly in humans. Here, to shed light on the so-far unknown human thymic peptide repertoire, we analyse peptides eluted from isolated thymic dendritic cells, dendritic cell-depleted antigen-presenting cells and whole thymus. Bioinformatic analysis of the 842 identified natural major histocompatibility complex I and II ligands reveals significant cross-talk between major histocompatibility complex-class I and II pathways and differences in source protein representation between individuals as well as different antigen-presenting cells. Furthermore, several autoimmune- and tumour-related peptides, from enolase and vimentin for example, are presented in the healthy thymus. 302 peptides are directly derived from negatively selecting dendritic cells, thus providing the first global view of the peptide matrix in the human thymus that imposes self-tolerance in vivo.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Merz, Christina

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2041-1723

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Anita Dähler

Date Deposited:

16 Dec 2013 10:21

Last Modified:

13 Mar 2021 14:30

Publisher DOI:

10.1038/ncomms3039

PubMed ID:

23783831

BORIS DOI:

10.7892/boris.39625

URI:

https://boris.unibe.ch/id/eprint/39625

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