Motozono, Chihiro, Pearson, James A.  ORCID: https://orcid.org/0000-0002-2867-2269, De Leenheer, Evy, Rizkallah, Pierre J. ORCID: https://orcid.org/0000-0002-9290-0369, Beck, Konrad ORCID: https://orcid.org/0000-0001-5098-9484, Trimby, Andrew, Sewell, Andrew K. ORCID: https://orcid.org/0000-0003-3194-3135, Wong, F. Susan ORCID: https://orcid.org/0000-0002-2812-8845 and Cole, David K. ORCID: https://orcid.org/0000-0003-0028-9396
2015.
Distortion of the major histocompatibility complex class I binding groove to accommodate an insulin-derived 10-Mer peptide.
Journal of Biological Chemistry
290
(31)
, pp. 18924-18933.
10.1074/jbc.M114.622522
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Abstract
The non-obese diabetic mouse model of type 1 diabetes continues to be an important tool for delineating the role of T-cell-mediated destruction of pancreatic β-cells. However, little is known about the molecular mechanisms that enable this disease pathway. We show that insulin reactivity by a CD8+ T-cell clone, known to induce type 1 diabetes, is characterized by weak T-cell antigen receptor binding to a relatively unstable peptide-MHC. The structure of the native 9- and 10-mer insulin epitopes demonstrated that peptide residues 7 and 8 form a prominent solvent-exposed bulge that could potentially be the main focus of T-cell receptor binding. The C terminus of the peptide governed peptide-MHC stability. Unexpectedly, we further demonstrate a novel mode of flexible peptide presentation in which the MHC peptide-binding groove is able to “open the back door” to accommodate extra C-terminal peptide residues.
| Item Type: | Article |
|---|---|
| Date Type: | Publication |
| Status: | Published |
| Schools: | Schools > Dentistry Schools > Medicine Research Institutes & Centres > Systems Immunity Research Institute (SIURI) |
| Subjects: | R Medicine > R Medicine (General) |
| Additional Information: | This is an open access article under the CC-BY license. |
| Publisher: | American Society for Biochemistry and Molecular Biology |
| ISSN: | 0021-9258 |
| Funders: | Wellcome |
| Date of First Compliant Deposit: | 30 March 2016 |
| Date of Acceptance: | 17 June 2015 |
| Last Modified: | 05 Jan 2024 08:15 |
| URI: | https://orca.cardiff.ac.uk/id/eprint/75686 |
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