Antigen-Specific T Cell Analysis Reveals That Active Immune Responses to β Cell Antigens Are Focused on a Unique Set of Epitopes

被引:21
作者
Yang, Junbao [1 ]
Wen, Xiaomin [1 ]
Xu, Hengyu [1 ]
Torres-Chinn, Nadia [1 ]
Speake, Cate [1 ]
Greenbaum, Carla J. [1 ]
Nepom, Gerald T. [1 ]
Kwok, William W. [1 ,2 ]
机构
[1] Virginia Mason, Benaroya Res Inst, 1201 9th Ave, Seattle, WA 98101 USA
[2] Univ Washington, Dept Med, Seattle, WA 98109 USA
基金
美国国家卫生研究院;
关键词
SUBUNIT-RELATED PROTEIN; INSULIN EPITOPE; DIABETIC MICE; CD4(+); DESTRUCTION; AUTOANTIGEN; RECOGNIZE; MOUSE; CD4+; IDENTIFICATION;
D O I
10.4049/jimmunol.1601570
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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(+)beta 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 b 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.
引用
收藏
页码:91 / 96
页数:6
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