NDLI: Stable interactions and sustained TCR signaling characterize thymocyte-thymocyte interactions that support negative selection.

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Stable interactions and sustained TCR signaling characterize thymocyte-thymocyte interactions that support negative selection.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Taylor, Kayleigh T. Ross, Jenny O. Robey, Ellen A. Melichar, Heather J.
Description	Author Affiliation: Melichar HJ ( Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720.); Ross JO ( Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720.); Taylor KT ( Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720.); Robey EA ( Division of Immunology and Pathogenesis, Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720 erobey@berkeley.edu.)
Abstract	Negative selection is one of the primary mechanisms that render T cells tolerant to self. Thymic dendritic cells play an important role in negative selection, in line with their ability to induce migratory arrest and sustained TCR signals. Thymocytes themselves display self-peptide/MHC class I complexes, and although there is evidence that they can support clonal deletion, it is not clear whether they do so directly via stable cell-cell contacts and sustained TCR signals. In this study, we show that murine thymocytes can support surprisingly efficient negative selection of Ag-specific thymocytes. Furthermore, we observe that agonist-dependent thymocyte-thymocyte interactions occurred as stable, motile conjugates led by the peptide-presenting thymocyte and in which the trailing peptide-specific thymocyte exhibited persistent elevations in intracellular calcium concentration. These data confirm that self-Ag presentation by thymocytes is an additional mechanism to ensure T cell tolerance and further strengthen the correlation between stable cellular contacts, sustained TCR signals, and efficient negative selection.
ISSN	00221767
e-ISSN	15506606
DOI	10.4049/jimmunol.1400169
Journal	The Journal of Immunology
Issue Number	3
Volume Number	194
Language	English
Publisher	The American Association of Immunologists
Publisher Date	2015-02-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Cell Communication Clonal Deletion Clonal Selection, Antigen-mediated Receptors, Antigen, T-cell Metabolism Signal Transduction Thymocytes Immunology Animals Antigen Presentation Antigen-presenting Cells Dendritic Cells Mice Mice, Transgenic Peptides Protein Binding T-lymphocyte Subsets Research Support, N.i.h., Extramural Discipline Immunology
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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Stable interactions and sustained TCR signaling characterize thymocyte-thymocyte interactions that support negative selection.

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Stable interactions and sustained TCR signaling characterize thymocyte-thymocyte interactions that support negative selection.