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Citations to this article

The diabetogenic mouse MHC class II molecule I-Ag7 is endowed with a switch that modulates TCR affinity
Kenji Yoshida, … , Ian A. Wilson, Luc Teyton
Kenji Yoshida, … , Ian A. Wilson, Luc Teyton
Published April 19, 2010
Citation Information: J Clin Invest. 2010;120(5):1578-1590. https://doi.org/10.1172/JCI41502.
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Research Article Article has an altmetric score of 1

The diabetogenic mouse MHC class II molecule I-Ag7 is endowed with a switch that modulates TCR affinity

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Abstract

Genetic susceptibility to autoimmunity is frequently associated with specific MHC alleles. Diabetogenic MHC class II molecules, such as human HLA-DQ8 and mouse I-Ag7, typically have a small, uncharged amino acid residue at position 57 of their β chain (β57); this results in the absence of a salt bridge between β57 and Argα76, which is adjacent to the P9 pocket of the peptide-binding groove. However, the influence of Argα76 on the selection of the TCR repertoire remains unknown, particularly when the MHC molecule binds a peptide with a neutral amino acid residue at position P9. Here, we have shown that diabetogenic MHC class II molecules bound to a peptide with a neutral P9 residue primarily selected and expanded cells expressing TCRs bearing a negatively charged residue in the first segment of their complementarity determining region 3β. The crystal structure of one such TCR in complex with I-Ag7 bound to a peptide containing a neutral P9 residue revealed that a network of favorable long-range (greater than 4 Å) electrostatic interactions existed among Argα76, the neutral P9 residue, and TCR, which supported the substantially increased TCR/peptide-MHC affinity. This network could be modulated or switched to a lower affinity interaction by the introduction of a negative charge at position P9 of the peptide. Our results support the existence of a switch at residue β57 of the I-Ag7 and HLA-DQ8 class II molecules and potentially link normal thymic TCR selection with abnormal peripheral behavior.

Authors

Kenji Yoshida, Adam L. Corper, Rana Herro, Bana Jabri, Ian A. Wilson, Luc Teyton

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Total citations by year

Year: 2025 2024 2023 2022 2020 2019 2017 2016 2014 2013 2012 2011 2010 Total
Citations: 1 2 3 2 5 3 1 1 3 1 2 4 1 29
Citation information
This citation data is accumulated from CrossRef, which receives citation information from participating publishers, including this journal. Not all publishers participate in CrossRef, so this information is not comprehensive. Additionally, data may not reflect the most current citations to this article, and the data may differ from citation information available from other sources (for example, Google Scholar, Web of Science, and Scopus).

Citations to this article in year 2012 (2)

Title and authors Publication Year
On the perils of poor editing: regulation of peptide loading by HLA-DQ and H2-A molecules associated with celiac disease and type 1 diabetes
R Busch, AD Riva, AV Hadjinicolaou, W Jiang, T Hou, ED Mellins
Expert Reviews in Molecular Medicine 2012
Posttranslational Modifications of Proteins in Type 1 Diabetes: The Next Step in Finding the Cure?
JL Dunne, L Overbergh, AW Purcell, C Mathieu
Diabetes 2012

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