Antigen-specific T cell analysis reveals that active immune responses to β cell antigens are focused on a unique set of epitopes

J Yang, X Wen, H Xu, N Torres-Chinn… - The Journal of …, 2017 - journals.aai.org
J Yang, X Wen, H Xu, N Torres-Chinn, C Speake, CJ Greenbaum, GT Nepom, WW Kwok
The Journal of Immunology, 2017journals.aai.org
CD38 is an activation marker that is present on recently activated T cells, but absent on
resting memory T cells. In this study, we show that CD45RO+ CD38+ β cell Ag-specific
CD4+ T cells were present at higher frequencies in type 1 diabetes subjects compared with
those in healthy subjects. These results imply an ongoing β cell immunity years after onset of
diabetes and suggest these activated T cells have an active role in the disease process. The
Ag specificities of these activated T cells were determined by a novel CD154 T cell epitope …
Abstract
CD38 is an activation marker that is present on recently activated T cells, but absent on resting memory T cells. In this study, we show that CD45RO+ CD38+ β cell Ag-specific CD4+ T cells were present at higher frequencies in type 1 diabetes subjects compared with those in healthy subjects. These results imply an ongoing β cell immunity years after onset of diabetes and suggest these activated T cells have an active role in the disease process. The Ag specificities of these activated T cells were determined by a novel CD154 T cell epitope mapping assay. Although each patient usually had a unique set of epitopes recognized by these T cells, two epitopes, DR0401-restricted modified preproinsulin peptide 78–90 K88S and zinc transport 8 266–285, were repeatedly identified in multiple subjects. Identifying these T cells and their specific antigenic epitopes might provide immunotherapeutic targets for personalized therapies.
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