000 02813 am a22003133u 4500
042 _adc
100 1 0 _aElliot, Thomas A. E.
_eauthor
_92099
700 1 0 _aJennings, Emma K.
_eauthor
_92100
700 1 0 _aLecky, David A. J.
_eauthor
_92101
700 1 0 _aRouvray, Sophie
_eauthor
_92102
700 1 0 _aMackie, Gillian M.
_eauthor
_92103
700 1 0 _aScarfe, Lisa
_eauthor
_92104
700 1 0 _aSheriff, Lozan
_eauthor
_92105
700 1 0 _aOno, Masahiro
_eauthor
_92106
700 1 0 _aMaslowski, Kendle M.
_eauthor
_92107
700 1 0 _aBending, David
_eauthor
_92108
245 0 0 _aNur77-Tempo mice reveal T cell steady state antigen recognition
260 _c2022-12-22.
500 _a/pmc/articles/PMC7614040/
500 _a/pubmed/36704407
520 _aIn lymphocytes, Nr4a gene expression is specifically regulated by antigen receptor signalling, making them ideal targets for use as distal T cell receptor (TCR) reporters. Nr4a3-Timer of cell kinetics and activity (Tocky) mice are a ground-breaking tool to report TCR-driven Nr4a3 expression using Fluorescent Timer protein (FT). FT undergoes a time-dependent shift in its emission spectrum following translation, allowing for the temporal reporting of transcriptional events. Our recent work suggested that Nr4a1/Nur77 may be a more sensitive gene to distal TCR signals compared to Nr4a3, so we, therefore, generated Nur77-Timer-rapidly-expressed-in-lymphocytes (Tempo) mice that express FT under the regulation of Nur77. We validated the ability of Nur77-Tempo mice to report TCR and B cell receptor signals and investigated the signals regulating Nur77-FT expression. We found that Nur77-FT was sensitive to low-strength TCR signals, and its brightness was graded in response to TCR signal strength. Nur77-FT detected positive selection signals in the thymus, and analysis of FT expression revealed that positive selection signals are often persistent in nature, with most thymic Treg expressing FT Blue. We found that active TCR signals in the spleen are low frequency, but CD69(+) lymphoid T cells are enriched for FT Blue(+) Red(+) T cells, suggesting frequent TCR signalling. In non-lymphoid tissue, we saw a dissociation of FT protein from CD69 expression, indicating that tissue residency is not associated with tonic TCR signals. Nur77-Tempo mice, therefore, combine the temporal dynamics from the Tocky innovation with increased sensitivity of Nr4a1 to lower TCR signal strengths.
540 _a
540 _ahttps://creativecommons.org/licenses/by/4.0/This work is licensed under a CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/) International license.
546 _aen
690 _aArticle
655 7 _aText
_2local
786 0 _nDiscov Immunol
856 4 1 _uhttp://dx.doi.org/10.1093/discim/kyac009
_zConnect to this object online.
999 _c2002
_d2002