title: GAD65 is recognized by T-cells, but not by antibodies from NOD-mice.
abstract: Since the 64kDa-protein glutamic acid decarboxylase (GAD) is one of the major autoantigens in T-cell mediated Type 1 diabetes, its relevance as a T-cell antigen needs to be clarified. After isolation of splenic T-cells from non-obese diabetic (NOD) mice, a useful model for human Type 1 diabetes, we found that these T-cells proliferate spontaneously when incubated with human GAD65, but only marginally after incubation with GAD67, both recombinated in the baculovirus system. No effect was observed with non-diabetic NOD mice or with T-cells from H-2 identical NON-NOD-H-2g7 control mice. It has been published previously that NOD mice develop autoantibodies against a 64kDa protein detected with mouse beta cells. In immunoprecipitation experiments with sera from the same NOD mice and 35S-methionine-labelled GAD, no autoantibody binding could be detected. We conclude firstly that GAD65 is an important T-cell antigen which is relevant early in the development of Type 1 diabetes and secondly that there is an antigenic epitope in the human GAD65 molecule recognized by NOD T-cells, but not by NOD autoantibodies precipitating conformational epitopes. Our results therefore provide further evidence that GAD65 is a T-cell antigen in NOD mice, being possibly also involved in very early processes leading to the development of human Type 1 diabetes.
authors.affiliation: Department of Endocrinology, University Hospital Leipzig, FRG.
authors.forename: S
authors.initials: S
authors.lastname: Bieg
authors.forename: J
authors.initials: J
authors.lastname: Seissler
authors.forename: L
authors.initials: L
authors.lastname: Herberg
authors.forename: W
authors.initials: W
authors.lastname: Northemann
authors.forename: W A
authors.initials: WA
authors.lastname: Scherbaum
mesh_terms: D000818:Animals; D001323:Autoantibodies / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D011233:Precipitin Tests; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D001323:Autoantibodies; D005968:Glutamate Decarboxylase