Engineering mice to identify autoreactive t-cell antigens


Engineering mice to identify autoreactive t-cell antigens

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Access through your institution Buy or subscribe Now published in the journal _Science_, Professor Shimon Sakaguchi and colleagues present a novel method of autoantigen discovery and a


proof-of-principle, showing that the 60S ribosomal protein L23a (RPL23A) is an arthritogenic T-cell autoantigen. “By attenuation of T-cell receptor (TCR) signal strength,” says Sakaguchi, “T


cells recognizing ubiquitous self-antigens, which are normally deleted in the thymus by negative selection, are selected as a dominant repertoire and are causative of systemic autoimmune


diseases.” By engineering retrogenic mice to expand and isolate pathogenic TCR-expressing T cells, a method Sakaguchi says was pioneered by Dr Dario Vignali, the researchers were able to


examine a number of individual TCRs for their pathogenicity. Adding to this technique, Sakaguchi says, “We then came up with the idea that by reconstituting arthritis-bearing retrogenic mice


with B cells, autoantibodies thus produced by the 'help' of arthritogenic T cells would react with antigens recognized by the arthritogenic TCRs, circumventing other meticulous


ways of directly identifying self-peptides.” This is a preview of subscription content, access via your institution ACCESS OPTIONS Access through your institution Subscribe to this journal


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REFERENCES * Ito, Y. _ et al_. Detection of T cell responses to a ubiquitous cellular protein in autoimmune disease. _Science_ 346, 363–368 (2014) Article  CAS  Google Scholar  Download


references Authors * Nicholas J. Bernard View author publications You can also search for this author inPubMed Google Scholar RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS


ARTICLE CITE THIS ARTICLE Bernard, N. Engineering mice to identify autoreactive T-cell antigens. _Nat Rev Rheumatol_ 10, 697 (2014). https://doi.org/10.1038/nrrheum.2014.190 Download


citation * Published: 04 November 2014 * Issue Date: December 2014 * DOI: https://doi.org/10.1038/nrrheum.2014.190 SHARE THIS ARTICLE Anyone you share the following link with will be able to


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