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@ARTICLE{Raposo:142744,
author = {B. Raposo and P. Merky and C. Lundqvist and H. Yamada and
V. Urbonaviciute and C. Niaudet and J. Viljanen and J.
Kihlberg and B. Kyewski$^*$ and O. Ekwall and R. Holmdahl
and J. Bäcklund},
title = {{T} cells specific for post-translational modifications
escape intrathymic tolerance induction.},
journal = {Nature Communications},
volume = {9},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DKFZ-2019-00461},
pages = {353},
year = {2018},
abstract = {Establishing effective central tolerance requires the
promiscuous expression of tissue-restricted antigens by
medullary thymic epithelial cells. However, whether central
tolerance also extends to post-translationally modified
proteins is not clear. Here we show a mouse model of
autoimmunity in which disease development is dependent on
post-translational modification (PTM) of
the tissue-restricted self-antigen collagen type II. T
cells specific for the non-modified antigen undergo
efficient central tolerance. By contrast, PTM-reactive T
cells escape thymic selection, though the PTM variant
constitutes the dominant form in the periphery. This finding
implies that the PTM protein is absent in the thymus, or
present at concentrations insufficient to induce negative
selection of developing thymocytes and explains the lower
level of tolerance induction against the PTM antigen. As the
majority of self-antigens are post-translationally modified,
these data raise the possibility that T cells specific for
other self-antigens naturally subjected to PTM may escape
central tolerance induction by a similar mechanism.},
keywords = {Autoantigens (NLM Chemicals) / Collagen Type II (NLM
Chemicals)},
cin = {D090},
ddc = {500},
cid = {I:(DE-He78)D090-20160331},
pnm = {314 - Tumor immunology (POF3-314)},
pid = {G:(DE-HGF)POF3-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:29367624},
pmc = {pmc:PMC5783942},
doi = {10.1038/s41467-017-02763-y},
url = {https://inrepo02.dkfz.de/record/142744},
}