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T cell activation and anergy to islet cell antigen in type I diabetes.

I Miyazaki, R K Cheung, R Gaedigk, M F Hui, J Van der Meulen, R V Rajotte and H M Dosch
J Immunol February 1, 1995, 154 (3) 1461-1469;
I Miyazaki
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R K Cheung
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R Gaedigk
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M F Hui
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J Van der Meulen
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R V Rajotte
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H M Dosch
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Abstract

Early exposure to cow milk proteins was linked to the development of type I diabetes by consistent epidemiology, and by feeding and tolerization studies in diabetes-prone rodents. Dietary BSA was suggested as the culprit because patients and relevant rodents have elevated anti-BSA Abs that precipitate the recently cloned protein, p69, from beta cell lysates. A total of 68 of 78 children with recent onset diabetes had BSA-reactive T cells at the time of diagnosis. Here we 1) map the fine specificity of these T cells, 2) delineate a homologous peptide sequence near the N-terminus of p69, and 3) demonstrate T cell recognition of this p69 sequence (T cell epitope p69, Tep69) by patient T cells. The Tep69 sequence is conserved in p69 of patients and diabetes-prone rodents. Whereas BSA triggers T cell proliferation, recombinant p69 and a synthetic Tep69 peptide induce early stages of T cell activation (IL-2R transcription) but insufficient IL-2 production and thus anergy. Exogenous IL-2 overrides anergy and allows proliferative expansion of p69-responsive T cells. In mixing experiments, p69 and Tep69 peptide prevented proliferative responses to BSA even at 100-fold smaller concentrations. These findings imply that high-affinity self-peptide triggers anergy, whereas low-affinity mimicry Ag triggers proliferative expansion of these T cells. This implies a disease model in which mimicry Ag would rescue autoreactive cells from ablation by self-Ag.

  • Copyright © 1995 by American Association of Immunologists
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The Journal of Immunology
Vol. 154, Issue 3
1 Feb 1995
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T cell activation and anergy to islet cell antigen in type I diabetes.
I Miyazaki, R K Cheung, R Gaedigk, M F Hui, J Van der Meulen, R V Rajotte, H M Dosch
The Journal of Immunology February 1, 1995, 154 (3) 1461-1469;

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T cell activation and anergy to islet cell antigen in type I diabetes.
I Miyazaki, R K Cheung, R Gaedigk, M F Hui, J Van der Meulen, R V Rajotte, H M Dosch
The Journal of Immunology February 1, 1995, 154 (3) 1461-1469;
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