Translational mini-review series on type 1 diabetes: Systematic analysis of T cell epitopes in autoimmune diabetes

被引:217
作者
Di Lorenzo, T. P.
Peakman, M.
Roep, B. O.
机构
[1] Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10467 USA
[2] Albert Einstein Coll Med, Dept Med, Div Endocrinol, Bronx, NY 10467 USA
[3] Kings Coll London, Dept Immunobiol, Sch Med, London WC2R 2LS, England
[4] Leiden Univ, Med Ctr, Dept Immunoharmatol & Blood Transfus, NL-2300 RA Leiden, Netherlands
关键词
antigens/epitopes; autoimmunity; diabetes; GLUTAMIC-ACID DECARBOXYLASE; RECENT-ONSET IDDM; PHOSPHATASE-LIKE MOLECULE; SUBUNIT-RELATED PROTEIN; AUTOANTIGEN IA-2; NOD MICE; PROLIFERATIVE RESPONSES; IMMUNODOMINANT EPITOPE; PROINSULIN EPITOPES; CYTOKINE PRODUCTION;
D O I
10.1111/j.1365-2249.2006.03244.x
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
T cell epitopes represent the molecular code words through which the adaptive immune system communicates. In the context of a T cell-mediated autoimmune disease such as type 1 diabetes, CD4 and CD8 T cell recognition of islet autoantigenic epitopes is a key step in the autoimmune cascade. Epitope recognition takes place during the generation of tolerance, during its loss as the disease process is initiated, and during epitope spreading as islet cell damage is perpetuated. Epitope recognition is also a potentially critical element in therapeutic interventions such as antigen-specific immunotherapy. T cell epitope discovery, therefore, is an important component of type 1 diabetes research, in both human and murine models. With this in mind, in this review we present a comprehensive guide to epitopes that have been identified as T cell targets in autoimmune diabetes. Targets of both CD4 and CD8 T cells are listed for human type 1 diabetes, for humanized [human leucocyte antigen (HLA)-transgenic] mouse models, and for the major spontaneous disease model, the non-obese diabetic (NOD) mouse. Importantly, for each epitope we provide an analysis of the relative stringency with which it has been identified, including whether recognition is spontaneous or induced and whether there is evidence that the epitope is generated from the native protein by natural antigen processing. This analysis provides an important resource for investigating diabetes pathogenesis, for developing antigen-specific therapies, and for developing strategies for T cell monitoring during disease development and therapeutic intervention.
引用
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页码:1 / 16
页数:16
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