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: | 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: | 17 Nov 2024 03:30 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/100738 |
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