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Autoantibodies and associated T-cell responses to determinants within the 831-860 region of the autoantigen IA-2 in Type 1 diabetes.
Weenink, S M; Lo, J; Stephenson, C R; McKinney, P A; Ananieva-Jordanova, R; Rees Smith, B; Furmaniak, J; Tremble, J M; Bodansky, H J; Christie, M R.
Afiliación
  • Weenink SM; Diabetes Research Group, Division of Reproduction & Endocrinology, 2nd Floor Hodgkin Building, King's College London, Guy's Campus, London, United Kingdom.
J Autoimmun ; 33(2): 147-54, 2009 Sep.
Article en En | MEDLINE | ID: mdl-19447008
B-cells influence T-cell reactivity by facilitating antigen presentation, but the role of autoantibody-secreting B-cells in regulating T-cell responses in Type 1 diabetes is poorly defined. The aims of this study were to characterise epitopes on the IA-2 autoantigen for three monoclonal antibodies from diabetic patients by amino acid substitutions of selected residues of IA-2, establish contributions of these epitopes to binding of serum antibodies in Type 1 diabetes and relate B- and T-cell responses to overlapping determinants on IA-2. The monoclonal antibodies recognised overlapping epitopes, with residues within the 831-860 region of IA-2 contributing to binding; substitution of Glu836 inhibited binding of all three antibodies. Monoclonal antibody Fab fragments and substitution of residues within the 831-836 region blocked serum antibody binding to an IA-2 643-937 construct. IL-10-secreting T-cells responding to peptides within the 831-860 region were detected by cytokine-specific ELISPOT in diabetic patients and responses to 841-860 peptide were associated with antibodies to the region of IA-2 recognised by the monoclonal antibodies. The study identifies a region of IA-2 frequently recognised by antibodies in Type 1 diabetes and demonstrates that these responses are associated with T-cells secreting IL-10 in response to a neighbouring determinant.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autoanticuerpos / Autoantígenos / Linfocitos T / Epítopos de Linfocito T / Diabetes Mellitus Tipo 1 / Proteínas Tirosina Fosfatasas Clase 8 Similares a Receptores Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Child / Female / Humans / Infant / Male Idioma: En Revista: J Autoimmun Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2009 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Reino Unido
Texto completo
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XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Autoanticuerpos / Autoantígenos / Linfocitos T / Epítopos de Linfocito T / Diabetes Mellitus Tipo 1 / Proteínas Tirosina Fosfatasas Clase 8 Similares a Receptores Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Adolescent / Adult / Child / Female / Humans / Infant / Male Idioma: En Revista: J Autoimmun Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2009 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Reino Unido