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

Eleni Adamopoulou, Stefan Tenzer, Nina Hillen, Paula Klug, Ioanna A. Rota, Silvia Tietz, Madlen Gebhardt, Stefan Stevanovic, Hansjörg Schild, Eva Tolosa, Arthur Melms and Christina Stoeckle ()
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Eleni Adamopoulou: Hertie Institute for Clinical Brain Research, 72076 Tübingen Germany
Stefan Tenzer: Institute for Immunology, University Medical Center of the Johannes Gutenberg University of Mainz, 55131 Mainz, Germany
Nina Hillen: Institute of Cell Biology, University of Tübingen, 72076 Tübingen, Germany
Paula Klug: Hertie Institute for Clinical Brain Research, 72076 Tübingen Germany
Ioanna A. Rota: Hertie Institute for Clinical Brain Research, 72076 Tübingen Germany
Silvia Tietz: Hertie Institute for Clinical Brain Research, 72076 Tübingen Germany
Madlen Gebhardt: Hertie Institute for Clinical Brain Research, 72076 Tübingen Germany
Stefan Stevanovic: Institute of Cell Biology, University of Tübingen, 72076 Tübingen, Germany
Hansjörg Schild: Institute for Immunology, University Medical Center of the Johannes Gutenberg University of Mainz, 55131 Mainz, Germany
Eva Tolosa: Institute for Immunology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany
Arthur Melms: Hertie Institute for Clinical Brain Research, 72076 Tübingen Germany
Christina Stoeckle: Hertie Institute for Clinical Brain Research, 72076 Tübingen Germany

Nature Communications, 2013, vol. 4, issue 1, 1-9

Abstract: Abstract 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.

Date: 2013
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DOI: 10.1038/ncomms3039

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