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. ORCID: https://orcid.org/0000-0003-3194-3135, Peakman, Mark, Chakraborty, Arup K. and Huseby, Eric S. 2016. Hydrophobic CDR3 residues promote the development of self-reactive T cells. Nature Immunology 17 , pp. 946-955. 10.1038/ni.3491

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Abstract

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:	14 Nov 2023 12:08
URI:	https://orca.cardiff.ac.uk/id/eprint/100738

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