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Hydrophobic CDR3 residues promote the development of self-reactive T cells

Stadinski, Brian D., Shekhar, Karthik, Gomez-Tourio, Iria, Jung, Jonathan, Sasaki, Katsuhiro, Sewell, Andrew K., Peakman, Mark, Chakraborty, Arup K. and Huseby, Eric S. 2016. Hydrophobic CDR3 residues promote the development of self-reactive T cells. Nature Immunology 17 (8) , pp. 946-955. 10.1038/ni.3491

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Studies of individual T cell antigen receptors (TCRs) have shed some light on structural features that underlie self-reactivity. However, the general rules that can be used to predict whether TCRs are self-reactive have not been fully elucidated. Here we found that the interfacial hydrophobicity of amino acids at positions 6 and 7 of the complementarity-determining region CDR3β robustly promoted the development of self-reactive TCRs. This property was found irrespective of the member of the β-chain variable region (Vβ) family present in the TCR or the length of the CDR3β. An index based on these findings distinguished Vβ2+, Vβ6+ and Vβ8.2+ regulatory T cells from conventional T cells and also distinguished CD4+ T cells selected by the major histocompatibility complex (MHC) class II molecule I-Ag7 (associated with the development of type 1 diabetes in NOD mice) from those selected by a non–autoimmunity-promoting MHC class II molecule I-Ab. Our results provide a means for distinguishing normal T cell repertoires versus autoimmunity-prone T cell repertoires.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Subjects: R Medicine > R Medicine (General)
Uncontrolled Keywords: Central tolerance; Next-generation sequencing; T-cell receptor; Type 1 diabetes; X-ray crystallography
Publisher: Nature Publishing Group
ISSN: 1529-2908
Date of First Compliant Deposit: 23 May 2017
Date of Acceptance: 12 May 2016
Last Modified: 05 Jun 2017 15:04

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