Whether and how thymic tolerance to tissue-restricted antigens (TRA) could be achieved posed a conundrum until Klein and colleagues discovered that medullary thymic epithelial cells were capable of bursts of TRA expression.
References
Kappler, J. W., Roehm, N. & Marrack, P. Cell 49, 273–280 (1987).
Kisielow, P., Blüthmann, H., Staerz, U. D., Steinmetz, M. & von Boehmer, H. Nature 333, 742–746 (1988).
Arnold, B., Schönrich, G. & Hämmerling, G. J. Immunol. Today 14, 12–14 (1993).
Klein, L., Klein, T., Rüther, U. & Kyewski, B. J. Exp. Med. 188, 5–16 (1998).
Egwuagu, C. E., Charukamnoetkanok, P. & Gery, I. J. Immunol. 159, 3109–3112 (1997).
Heath, V. L., Moore, N. C., Parnell, S. M. & Mason, D. W. J. Autoimmun. 11, 309–318 (1998).
Jolicoeur, C., Hanahan, D. & Smith, K. M. Proc. Natl Acad. Sci. USA 91, 6707–6711 (1994).
Pugliese, A. et al. Nat. Genet. 15, 293–297 (1997).
Chelly, J., Concordet, J. P., Kaplan, J. C. & Kahn, A. Proc. Natl Acad. Sci. USA 86, 2617–2621 (1989).
Sarkar, G. & Sommer, S. S. Science 244, 331–334 (1989).
Linsk, R., Gottesman, M. & Pernis, B. Science 246, 261 (1989).
Klein, L. & Kyewski, B. J. Mol. Med. (Berl.) 78, 483–494 (2000).
Hanahan, D. Curr. Opin. Immunol. 10, 656–662 (1998).
Smith, K. M., Olson, D. C., Hirose, R. & Hanahan, D. Int. Immunol. 9, 1355–1365 (1997).
Derbinski, J., Schulte, A., Kyewski, B. & Klein, L. Nat. Immunol. 2, 1032–1039 (2001).
Klein, L., Roettinger, B. & Kyewski, B. Eur. J. Immunol. 31, 2476–2486 (2001).
Brennecke, P. et al. Nat. Immunol. 16, 933–941 (2015).
Meredith, M., Zemmour, D., Mathis, D. & Benoist, C. Nat. Immunol. 16, 942–949 (2015).
Sansom, S. N. et al. Genome Res. 24, 1918–1931 (2014).
Anderson, M. S. et al. Science 298, 1395–1401 (2002).
Mathis, D. & Benoist, C. Annu. Rev. Immunol. 27, 287–312 (2009).
Peterson, P., Org, T. & Rebane, A. Nat. Rev. Immunol. 8, 948–957 (2008).
Aichinger, M., Wu, C., Nedjic, J. & Klein, L. J. Exp. Med. 210, 287–300 (2013).
Hinterberger, M. et al. Nat. Immunol. 11, 512–519 (2010).
Nedjic, J., Aichinger, M., Emmerich, J., Mizushima, N. & Klein, L. Nature 455, 396–400 (2008).
Koble, C. & Kyewski, B. J. Exp. Med. 206, 1505–1513 (2009).
Le Borgne, M. et al. Nat. Immunol. 10, 823–830 (2009).
Aschenbrenner, K. et al. Nat. Immunol. 8, 351–358 (2007).
Perry, J. S. A. et al. Immunity 41, 414–426 (2014).
Yang, S., Fujikado, N., Kolodin, D., Benoist, C. & Mathis, D. Science 348, 589–594 (2015).
Legoux, F. P. et al. Immunity 43, 896–908 (2015).
Malhotra, D. et al. Nat. Immunol. 17, 187–195 (2016).
Hassler, T. et al. Proc. Natl Acad. Sci. USA 116, 18537–18543 (2019).
Klein, L., Kyewski, B., Allen, P. M. & Hogquist, K. A. Nat. Rev. Immunol. 14, 377–391 (2014).
Klein, L. Nat. Immunol. 19, 509 (2018).
Acknowledgements
This article is dedicated to the memory of Bruno Kyewski. I thank all the members of my team who have worked with me over the years and apologize to those who embarked on projects that actually got less exciting when things stopped falling into place.
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Klein, L. Recollections of the discovery of promiscuous antigen expression in mTECs. Nat Immunol 21, 1303–1305 (2020). https://doi.org/10.1038/s41590-020-0771-9
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DOI: https://doi.org/10.1038/s41590-020-0771-9
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