Epitopes described in "T cell autoreactivity to proinsulin epitopes in diabetic patients and healthy subjects."

Article Authors:G Semana; R Gausling; R A Jackson; D A Hafler
Article Title:T cell autoreactivity to proinsulin epitopes in diabetic patients and healthy subjects.
Reference Detail
Reference ID:1007567
Abstract:We investigated the immune response to proinsulin, a potential autoantigen in IDDM secreted exclusively by pancreatic beta-cells. A total of 2,142 short-term cell lines were generated from 19 individuals; seven IDDM patients at the disease onset and 12 control subjects. No increase in the frequency of proinsulin reactive cells was observed in the IDDM group. To define proinsulin epitopes, proliferative responses of proinsulin-specific lines were examined against 10 overlapping 15 amino acid peptides encompassing the human proinsulin sequence. The predominant immune response was directed against the proinsulin p35-50 peptide located in the (C) connecting peptide between the alpha- and beta-chain of insulin. Recognition of the proinsulin p35-50 peptide could be shown by generating specific T cell clones against the peptide. However, unlike responses to other tissue-specific autoantigens there were only low proliferative responses to proinsulin as measured by 3H-thymidine incorporation. This low reactivity may be partially explained by the location of the p35-50 peptide in the C-peptide which is released into the circulation and therefore, may induce a clonal anergy of T reactive cells. However, the significantly higher 3H-thymidine incorporation after CD3-CD28 triggering showed that peptide specific T cells were capable of a significant response with a stronger TCR signal.
Affiliations:Center of Neurologic Diseases, Brigham and Women's Hospital, Laboratory of Molecular Immunology, Boston, MA, USA. Gilbert.Semana@univ-rennes1.fr
Reference Type:Literature
PubMed ID:10330297
Journal:J Autoimmun
Journal Volume:12
Article Pages:259-67
Journal ISSN:0896-8411
Article Chemical List:Autoantigens;Peptide Fragments;Proinsulin
Article MeSH List:Amino Acid Sequence; Autoantigens(immunology ); Cell Line; Diabetes Mellitus, Type 1(immunology ); Epitope Mapping; Humans; Molecular Sequence Data; Peptide Fragments(immunology ); Proinsulin(immunology ); T-Lymphocytes(immunology )
Curation Last Updated:2015-01-27 19:52:57