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Corrigendum Free access | 10.1172/JCI89919

Hotspot autoimmune T cell receptor binding underlies pathogen and insulin peptide cross-reactivity

David K. Cole, Anna M. Bulek, Garry Dolton, Andrea J. Schauenberg, Barbara Szomolay, William Rittase, Andrew Trimby, Prithiviraj Jothikumar, Anna Fuller, Ania Skowera, Jamie Rossjohn, Cheng Zhu, John J. Miles, Mark Peakman, Linda Wooldridge, Pierre J. Rizkallah, and Andrew K. Sewell

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Published August 15, 2016 - More info

Published in Volume 126, Issue 9 on September 1, 2016
J Clin Invest. 2016;126(9):3626–3626. https://doi.org/10.1172/JCI89919.
Copyright © 2016, American Society for Clinical Investigation
Published August 15, 2016 - Version history
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Related article:

Hotspot autoimmune T cell receptor binding underlies pathogen and insulin peptide cross-reactivity
David K. Cole, … , Pierre J. Rizkallah, Andrew K. Sewell
David K. Cole, … , Pierre J. Rizkallah, Andrew K. Sewell
Research Article Autoimmunity Immunology

Hotspot autoimmune T cell receptor binding underlies pathogen and insulin peptide cross-reactivity

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Abstract

The cross-reactivity of T cells with pathogen- and self-derived peptides has been implicated as a pathway involved in the development of autoimmunity. However, the mechanisms that allow the clonal T cell antigen receptor (TCR) to functionally engage multiple peptide–major histocompatibility complexes (pMHC) are unclear. Here, we studied multiligand discrimination by a human, preproinsulin reactive, MHC class-I–restricted CD8+ T cell clone (1E6) that can recognize over 1 million different peptides. We generated high-resolution structures of the 1E6 TCR bound to 7 altered peptide ligands, including a pathogen-derived peptide that was an order of magnitude more potent than the natural self-peptide. Evaluation of these structures demonstrated that binding was stabilized through a conserved lock-and-key–like minimal binding footprint that enables 1E6 TCR to tolerate vast numbers of substitutions outside of this so-called hotspot. Highly potent antigens of the 1E6 TCR engaged with a strong antipathogen-like binding affinity; this engagement was governed though an energetic switch from an enthalpically to entropically driven interaction compared with the natural autoimmune ligand. Together, these data highlight how T cell cross-reactivity with pathogen-derived antigens might break self-tolerance to induce autoimmune disease.

Authors

David K. Cole, Anna M. Bulek, Garry Dolton, Andrea J. Schauenberg, Barbara Szomolay, William Rittase, Andrew Trimby, Prithiviraj Jothikumar, Anna Fuller, Ania Skowera, Jamie Rossjohn, Cheng Zhu, John J. Miles, Mark Peakman, Linda Wooldridge, Pierre J. Rizkallah, Andrew K. Sewell

×

Original citation: J Clin Invest. 2016;126(6):2191–2204. doi:10.1172/JCI85679.

Citation for this corrigendum: J Clin Invest. 2016;126(9):3626. doi:10.1172/JCI89919.

The original publication incorrectly stated that a peptide with the sequence YQFGPDFPTA was used as one of the altered peptide ligands. The correct sequence is YQFGPDFPIA. The online version of the article has been updated with the correct sequence. This error appeared in the following parts of the manuscript:

Methods, “Crystal structure determination”

Figure 1B and legend

Figure 2 legend

Figure 5 legend

Figure 6G and legend

Figure 7 legend

Figure 8 legend

Table 1

The authors regret the error.

Footnotes

See the related article beginning on page 2191.

Version history
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  • Version 2 (September 1, 2016): No description

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