GAD65-specific autoantibodies enhance the presentation of an immunodominant T-cell epitope from GAD65

Research output: Contribution to journalArticle

Standard

GAD65-specific autoantibodies enhance the presentation of an immunodominant T-cell epitope from GAD65. / af Hällström-Reijonen, Charlotta; Daniels, Terri L; Lernmark, A.; Nepom, Gerald T.

In: Diabetes, Vol. 49, No. 10, 2000, p. 1621-1626.

Research output: Contribution to journalArticle

Harvard

af Hällström-Reijonen, C, Daniels, TL, Lernmark, A & Nepom, GT 2000, 'GAD65-specific autoantibodies enhance the presentation of an immunodominant T-cell epitope from GAD65', Diabetes, vol. 49, no. 10, pp. 1621-1626.

APA

af Hällström-Reijonen, C., Daniels, T. L., Lernmark, A., & Nepom, G. T. (2000). GAD65-specific autoantibodies enhance the presentation of an immunodominant T-cell epitope from GAD65. Diabetes, 49(10), 1621-1626.

CBE

MLA

Vancouver

Author

af Hällström-Reijonen, Charlotta ; Daniels, Terri L ; Lernmark, A. ; Nepom, Gerald T. / GAD65-specific autoantibodies enhance the presentation of an immunodominant T-cell epitope from GAD65. In: Diabetes. 2000 ; Vol. 49, No. 10. pp. 1621-1626.

RIS

TY - JOUR

T1 - GAD65-specific autoantibodies enhance the presentation of an immunodominant T-cell epitope from GAD65

AU - af Hällström-Reijonen, Charlotta

AU - Daniels, Terri L

AU - Lernmark, A.

AU - Nepom, Gerald T

PY - 2000

Y1 - 2000

N2 - GAD65 autoantibodies (GAD65Ab) are highly prevalent in type 1 diabetes, but their functional role in the pathogenesis of the disease and their relationship to T-cell reactivity to GAD65 is still unclear. We tested the hypothesis that GAD65Ab modulate presentation of GAD65 to T-cells. T-cell hybridoma T33.1, which recognizes the GAD65 274-286 epitope in the context of HLA-DRB1*0401, was incubated with antigen-presenting cells exposed to recombinant human GAD65 alone or complexed with GAD65Ab+ or GAD65Ab- sera. Stimulation of the T33.1 hybridoma was greatly enhanced by multiple GAD65Ab+ sera. The enhancement effect was most prominent with sera from patients with high GAD65 autoantibody levels. Sera from GAD65Ab- subjects had no effect. The correlation between T-cell stimulation and GAD65Ab levels was not absolute, suggesting that other variables such as autoantibody recognition of different regions of GAD65 and variable effects on processing of the 274-286 epitope may contribute. Uptake of antibody-complexed GAD65 was Fc receptor (FcR)-mediated because the enhancement of presentation was inhibited by monoclonal antibodies against FcR. Our results support the hypothesis that GAD65Ab modulate presentation of GAD65 to T-cells. Increased antigen uptake and heterogeneity in the autoantibody specificity may provide a mechanism for antibody-facilitated T-cell response influencing the progression of type 1 diabetes.

AB - GAD65 autoantibodies (GAD65Ab) are highly prevalent in type 1 diabetes, but their functional role in the pathogenesis of the disease and their relationship to T-cell reactivity to GAD65 is still unclear. We tested the hypothesis that GAD65Ab modulate presentation of GAD65 to T-cells. T-cell hybridoma T33.1, which recognizes the GAD65 274-286 epitope in the context of HLA-DRB1*0401, was incubated with antigen-presenting cells exposed to recombinant human GAD65 alone or complexed with GAD65Ab+ or GAD65Ab- sera. Stimulation of the T33.1 hybridoma was greatly enhanced by multiple GAD65Ab+ sera. The enhancement effect was most prominent with sera from patients with high GAD65 autoantibody levels. Sera from GAD65Ab- subjects had no effect. The correlation between T-cell stimulation and GAD65Ab levels was not absolute, suggesting that other variables such as autoantibody recognition of different regions of GAD65 and variable effects on processing of the 274-286 epitope may contribute. Uptake of antibody-complexed GAD65 was Fc receptor (FcR)-mediated because the enhancement of presentation was inhibited by monoclonal antibodies against FcR. Our results support the hypothesis that GAD65Ab modulate presentation of GAD65 to T-cells. Increased antigen uptake and heterogeneity in the autoantibody specificity may provide a mechanism for antibody-facilitated T-cell response influencing the progression of type 1 diabetes.

UR - http://www.scopus.com/inward/record.url?scp=0033815194&partnerID=8YFLogxK

M3 - Article

C2 - 11016444

AN - SCOPUS:0033815194

VL - 49

SP - 1621

EP - 1626

JO - Diabetes

JF - Diabetes

SN - 1939-327X

IS - 10

ER -