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Identification of Hybrid Insulin Peptides (HIPs) in Mouse and Human Islets by Mass Spectrometry
journal contribution
posted on 2018-12-25, 00:00 authored by T. Aaron Wiles, Roger Powell, Cole Robert Michel, K. Scott Beard, Anita Hohenstein, Brenda Bradley, Nichole Reisdorph, Kathryn Haskins, Thomas DelongWe
recently discovered hybrid insulin peptides (HIPs) as a novel
class of post-translationally modified peptides in murine-derived
beta cell tumors, and we demonstrated that these molecules are autoantigens
in type 1 diabetes (T1D). A HIP consists of an insulin fragment linked
to another secretory granule peptide via a peptide bond. We verified
that autoreactive CD4 T cells in both mouse and human autoimmune diabetes
recognize these modified peptides. Here, we use mass spectrometric
analyses to confirm the presence of HIPs in both mouse and human pancreatic
islets. We also present criteria for the confident identification
of these peptides. This work supports the hypothesis that HIPs are
autoantigens in human T1D and provides a foundation for future efforts
to interrogate this previously unknown component of the beta cell
proteome.