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Publication Abstract from PubMed

The NOD mouse model of type 1 diabetes (T1D) continues to be an important tool for delineating the role of T-cell-mediated destruction of pancreatic beta-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 T1D is characterised by weak T cell antigen receptor (TCR) binding to a relatively unstable peptide-major histocompatibility complex (pMHC). The structure of the native 9-mer 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 TCR binding. The C-terminus of the peptide governed pMHC 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.

Distortion of the MHC class I binding groove to accommodate an insulin-derived 10-mer peptide.,Motozono C, Pearson JA, De Leenheer E, Rizkallah PJ, Beck K, Trimby A, Sewell AK, Wong FS, Cole DK J Biol Chem. 2015 Jun 17. pii: jbc.M114.622522. PMID:26085090^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.