Restricted islet-cell reactive T cell repertoire of early pancreatic islet infiltrates in NOD mice

被引:59
作者
Baker, FJ
Lee, M
Chien, YH
Davis, MM [1 ]
机构
[1] Stanford Univ, Howard Hughes Med Inst, Sch Med, Stanford, CA 94305 USA
[2] Stanford Univ, Dept Microbiol & Immunol, Sch Med, Stanford, CA 94305 USA
关键词
D O I
10.1073/pnas.142284899
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The mechanisms responsible for initiating autoimmune diabetes remain obscure. Here, we describe a method for identifying both the alpha- and beta-chains of the T cell receptor (TCR) from individual pancreatic islet-infiltrating T cells at the earliest stages of disease in nonobese diabetic mice (NOD). Analysis of the TCR repertoire of these early islet infiltrates reveals enrichment for a small subset of TCR sequences. Reconstitution of these TCR in vitro demonstrates that these receptors confer reactivity to islet cells but not to the well characterized autoantigens, glutamic acid decarboxylase (GAD65) and insulin. Thus, autoimmune diabetes in NOD may be initiated by a limited number of antigens distinct from GAD65 and insulin.
引用
收藏
页码:9374 / 9379
页数:6
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