GAD65-specific autoantibodies enhance the presentation of an immunodominant T-cell epitope from GAD65
(2000) In Diabetes 49(10). p.1621-1626- Abstract
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... (More)
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.
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- author
- af Hällström-Reijonen, Charlotta ; Daniels, Terri L ; Lernmark, A. LU and Nepom, Gerald T
- publishing date
- 2000
- type
- Contribution to journal
- publication status
- published
- in
- Diabetes
- volume
- 49
- issue
- 10
- pages
- 6 pages
- publisher
- American Diabetes Association Inc.
- external identifiers
-
- scopus:0033815194
- pmid:11016444
- ISSN
- 0012-1797
- language
- English
- LU publication?
- no
- id
- 96ce042e-9215-4796-9932-ed1b8ff5d5c6
- date added to LUP
- 2017-09-06 15:15:15
- date last changed
- 2024-03-13 08:19:10
@article{96ce042e-9215-4796-9932-ed1b8ff5d5c6, abstract = {{<p>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<sup>+</sup> or GAD65Ab<sup>-</sup> sera. Stimulation of the T33.1 hybridoma was greatly enhanced by multiple GAD65Ab<sup>+</sup> sera. The enhancement effect was most prominent with sera from patients with high GAD65 autoantibody levels. Sera from GAD65Ab<sup>-</sup> 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.</p>}}, author = {{af Hällström-Reijonen, Charlotta and Daniels, Terri L and Lernmark, A. and Nepom, Gerald T}}, issn = {{0012-1797}}, language = {{eng}}, number = {{10}}, pages = {{1621--1626}}, publisher = {{American Diabetes Association Inc.}}, series = {{Diabetes}}, title = {{GAD65-specific autoantibodies enhance the presentation of an immunodominant T-cell epitope from GAD65}}, volume = {{49}}, year = {{2000}}, }