Selective Immunotargeting of Pathogenic CD8 T Cells of Type 1 Diabetes Patients

To obtain proof-of-principle of our approach we have initiated tight collaboration between the Laboratory of Immunology at MIGAL Galilee Research Institute, Kiryat Shmona (MIGAL) and Breinin Center for Type 1 Diabetes and Endocrinology at the Ziv Medical Center in Safed (Ziv). In this study we will first identify carriers of the HLA-A0201 allele among pediatric and young adult T1D patients at Ziv. We will then screen the T cell pool in the peripheral blood samples of these patients for CD8 T cells reactive against any of 3 known HLA-A0201-binding peptides associated with autoreactivity in T1D: Insulin beta chain 10-18, IGRP 265-73 and IGRP 222-230. The influenza virus-derived peptide MP 58-66 will serve as reference. Next we will isolate polyclonal CD8 T cells from blood samples of the same patients, activate and expand them ex-vivo and transfect them via electroporation with in-vitro-transcribed mRNA encoding the respective peptide/MHC/CD3-zeta construct(s). We will then perform co-culture experiments assessing the ability of the mRNA-transfected T cells to kill the autoreactive T cells of the same patient in a peptide-selective manner.