Characterising early disease phenotype to identifying significance of native and non-conventional epitopes and discovering novel neoepitopes in type 1 diabetes
PhD student: Norkhairin Yusuf
Supervisor at TUD: Michele Solimena
Supervisor at KCL: Timothy Tree, Mark Peakman
Start date: 03.10.2016
It is of vital importance to identify the autoantigens involved in triggering the destruction of insulin-producing β-islet cells by pathogenic T lymphocytes. New antigenic epitopes were established to be a product of preproinsulin peptide fusion that occurs in islet beta cells creating a highly immunogenic post-translational modification species called Hybrid Insulin Peptides (HIPs). Although post-translational modification is a well-known property of antigens in many autoimmune disorders, the identification and characterization of these modified peptides in Type 1 Diabetes is still at its infancy. The project aims to determine whether autoreactive CD8+ T cells that recognize HIPs are present in disease and could potentially be involved in breaking self-tolerance in patients. It seeks to discover and identify these HIPs presented by various high risk HLA Class I molecules and detect the autoreactive CD8+ T Cells in patients at various stages of the disease.
Publications:
Metabolic and immune effects of immunotherapy with proinsulin peptide in human new-onset type 1 diabetes. M. Alhadj Ali, Y.F. Liu, S. Arif, D. Tatovic, H. Shariff, V.B. Gibson, N. Yusuf, R. Baptista, M. Eichmann, N. Petrov, S. Heck, J.H.M. Yang, T.I.M. Tree, I. Pujol-Autonell, L. Yeo, L.R. Baumard, R. Stenson, A. Howell, A. Clark, Z. Boult, J. Powrie, L. Adams, F.S. Wong, S. Luzio, G. Dunseath, K. Green, A. O'Keefe, G. Bayly, N. Thorogood, R. Andrews, N. Leech, F. Joseph, S. Nair, S. Seal, H. Cheung, C. Beam, R. Hills, M. Peakman, C.M. Dayan. Sci Transl Med. 2017;9:eaaf7779.
Molecular Pathways for Immune Recognition of Preproinsulin Signal Peptide in Type 1 Diabetes. D. Kronenberg-Versteeg, M. Eichmann, M.A. Russell, A. de Ru, B. Hehn, N. Yusuf, P.A. van Veelen, S.J. Richardson, N.G. Morgan, M.K. Lemberg, M. Peakman. Diabetes. 2018;67:687-696.
Proinsulin peptide promotes autoimmune diabetes in a novel HLA-DR3-DQ2-transgenic murine model of spontaneous disease. J. Verhagen, N. Yusuf, E.L. Smith, E.M. Whettlock, K. Naran, S. Arif, M. Peakman. Diabetologia. 2019;62:2252-2261.
Mapping T Cell Responses to Native and Neo-Islet Antigen Epitopes in at Risk and Type 1 Diabetes Subjects. S. Arif, I. Pujol-Autonell, Y. Kamra, E. Williams, N. Yusuf, C. Domingo-Vila, Y. Shahrabi, E. Pollock, L. Khatri, M. Peakman, T. Tree, A. Lorenc. Front Immunol. 2021, 12:675746.