Thymoproteasome and peptidic self View Full Text


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Article Info

DATE

2019-03

AUTHORS

Yousuke Takahama, Izumi Ohigashi, Shigeo Murata, Keiji Tanaka

ABSTRACT

Positive selection of T cells in the thymus is induced by low-affinity TCR recognition of self-peptide-MHC complexes expressed by cortical thymic epithelial cells (cTECs). cTECs express a specialized type of proteasomes, the thymoproteasome, which generates a unique spectrum of MHC class I-associated peptides and plays a critical role in thymic positive selection of CD8+ T cells. However, it remains unclear how the thymoproteasome contributes to the thymic positive selection. More than 30 years ago, the "peptidic self" hypothesis proposed that TCRs recognize MHC-presented peptides only, without interacting with MHC molecules, which turned out to be incorrect. Interestingly, however, by implying that a set of MHC-associated peptides forms immunological self, this hypothesis also predicted that positive selection in the thymus is the primary immune response to "foreign epitope" peptides during T cell development. The thymoproteasome-dependent unique self-peptides may create those foreign epitope peptides displayed in the thymus for positive selection of T cells. More... »

PAGES

217-221

References to SciGraph publications

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  • 2015-12. Thymoproteasomes produce unique peptide motifs for positive selection of CD8+ T cells in NATURE COMMUNICATIONS
  • 2012-02. How the TCR balances sensitivity and specificity for the recognition of self and pathogens in NATURE IMMUNOLOGY
  • 2016-08. Specialized proteasome subunits have an essential role in the thymic selection of CD8+ T cells in NATURE IMMUNOLOGY
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  • 2015-10. TCR affinity for thymoproteasome-dependent positively selecting peptides conditions antigen responsiveness in CD8+ T cells in NATURE IMMUNOLOGY
  • 2015-01. The TCR's sensitivity to self peptide-MHC dictates the ability of naive CD8+ T cells to respond to foreign antigens in NATURE IMMUNOLOGY
  • 1977-09. In a radiation chimaera, host H–2 antigens determine immune responsiveness of donor cytotoxic cells in NATURE
  • 1996-11. Structure of the complex between human T-cell receptor, viral peptide and HLA-A2 in NATURE
  • 2014-03. Intrinsic CD4+ T cell sensitivity and response to a pathogen are set and sustained by avidity for thymic and peripheral complexes of self peptide and MHC in NATURE IMMUNOLOGY
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  • 1990-03. Role of self-peptides in positively selecting the T-cell repertoire in NATURE
  • 1985-09. Binding of immunogenic peptides to Ia histocompatibility molecules in NATURE
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00251-018-1081-3

    DOI

    http://dx.doi.org/10.1007/s00251-018-1081-3

    DIMENSIONS

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    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30324237


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