T cells specific for post-translational modifications escape intrathymic tolerance induction
View/ Open
Author
Merky, Patrick
Lundqvist, Christina
Yamada, Hisakata
Urbonaviciute, Vilma
Niaudet, Colin
Viljanen, Johan
Kihlberg, Jan
Kyewski, Bruno
Ekwall, Olov
Holmdahl, Rikard
Bäcklund, Johan
Note: Order does not necessarily reflect citation order of authors.
Published Version
https://doi.org/10.1038/s41467-017-02763-yMetadata
Show full item recordCitation
Raposo, B., P. Merky, C. Lundqvist, H. Yamada, V. Urbonaviciute, C. Niaudet, J. Viljanen, et al. 2018. “T cells specific for post-translational modifications escape intrathymic tolerance induction.” Nature Communications 9 (1): 353. doi:10.1038/s41467-017-02763-y. http://dx.doi.org/10.1038/s41467-017-02763-y.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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5783942/pdf/Terms of Use
This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAACitable link to this page
http://nrs.harvard.edu/urn-3:HUL.InstRepos:34868763
Collections
- HMS Scholarly Articles [17922]
Contact administrator regarding this item (to report mistakes or request changes)