title: A proinsulin 74-90-derived protease-resistant, altered peptide ligand increases TGF-beta 1 secretion in PBMC from patients with type 1 diabetes mellitus.
abstract: Proinsulin is a major diabetes-associated autoantigen. APL have been shown to manipulate the immune response of T cells. Here, we generated a lysosomal protease-resistant proinsulin 74-90-derived APL using a CS-directed amino acid modification approach. These prAPL activated TGF-beta 1 secretion in proinsulin-reactive T cells from PBMC of patients with T1D. We provide evidence that proinsulin-derived prAPL modulate the cytokine signature of proinsulin-reactive T cells at a micromolar range by increasing anti-inflammatory cytokines, including TGF-beta 1. Thus, the use of prAPL is a promising tool to mitigate autoaggressive T cells.
authors.affiliation: Division of Endocrinology and Diabetes, Department of Internal Medicine I, University Medical Center Ulm and Center of Excellence Metabolic Disorders, Baden-Württemberg, Ulm, Germany.
authors.forename: Denise
authors.initials: D
authors.lastname: van Aalst
authors.forename: Hubert
authors.initials: H
authors.lastname: Kalbacher
authors.forename: David
authors.initials: D
authors.lastname: Palesch
authors.forename: Fang
authors.initials: F
authors.lastname: Zou
authors.forename: Andreas
authors.initials: A
authors.lastname: Spyrantis
authors.forename: Silke
authors.initials: S
authors.lastname: Rosinger
authors.forename: Bernhard O
authors.initials: BO
authors.lastname: Boehm
authors.forename: Timo
authors.initials: T
authors.lastname: Burster
mesh_terms: D000595:Amino Acid Sequence; D001324:Autoantigens / Q000276:immunology; D002469:Cell Separation; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism*; D008024:Ligands; D008213:Lymphocyte Activation / Q000276:immunology; D008969:Molecular Sequence Data; D011384:Proinsulin / Q000737:chemistry / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000276:immunology / Q000378:metabolism*
chemical_list: D001324:Autoantigens; D008024:Ligands; D053773:Transforming Growth Factor beta1; D011384:Proinsulin