title: Cutting edge: vasostatin-1-derived peptide ChgA29-42 is an antigenic epitope of diabetogenic BDC2.5 T cells in nonobese diabetic mice.
abstract: Mechanistic and therapeutic insights in autoimmune diabetes would benefit from a more complete identification of relevant autoantigens. BDC2.5 TCR transgenic NOD mice express transgenes for TCR Vα1 and Vβ4 chains from the highly diabetogenic BDC2.5 CD4(+) T cell clone, which recognizes pancreatic β cell membrane Ags presented by NOD I-A(g7) MHC class II molecules. The antigenic epitope of BDC2.5 TCR is absent in β cells that do not express chromogranin A (ChgA) protein. However, characterization of the BDC2.5 epitope in ChgA has given inconclusive results. We have now identified a ChgA29-42 peptide within vasostatin-1, an N-terminal natural derivative of ChgA as the BDC2.5 TCR epitope. Having the necessary motif for binding to I-A(g7), it activates BDC2.5 T cells and induces an IFN-γ response. More importantly, adoptive transfer of naive BDC2.5 splenocytes activated with ChgA29-42 peptide transferred diabetes into NOD/SCID mice.
authors.affiliation: Centre for Human Immunology, University of Western Ontario, London, Ontario N6A 5C1, Canada.
authors.forename: Enayat
authors.initials: E
authors.lastname: Nikoopour
authors.forename: Christian
authors.initials: C
authors.lastname: Sandrock
authors.forename: Katrina
authors.initials: K
authors.lastname: Huszarik
authors.forename: Olga
authors.initials: O
authors.lastname: Krougly
authors.forename: Edwin
authors.initials: E
authors.lastname: Lee-Chan
authors.forename: Emma L
authors.initials: EL
authors.lastname: Masteller
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Bluestone
authors.forename: Bhagirath
authors.initials: B
authors.lastname: Singh
mesh_terms: D019264:Adoptive Transfer; D000595:Amino Acid Sequence; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D053379:Chromogranin A / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D018984:Epitopes, T-Lymphocyte / Q000008:administration & dosage / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology*
chemical_list: C506150:CHGA protein, human; D053379:Chromogranin A; D018984:Epitopes, T-Lymphocyte; D010446:Peptide Fragments; C064110:vasostatin I