Epitopes described in "CD4+ T cells recognize diverse epitopes within GAD65: implications for repertoire development and diabetes monitoring."

Article Authors:Junbao Yang; Eddie A James; Srinath Sanda; Carla Greenbaum; William W Kwok
Article Title:CD4+ T cells recognize diverse epitopes within GAD65: implications for repertoire development and diabetes monitoring.
Reference Detail
Reference ID:1025550
Abstract:Type 1 diabetes is associated with T-cell responses to -cell antigens such as GAD65. Single T-cell epitopes have been investigated for immune monitoring with some success, but multiple epitopes may be required to fully characterize responses in all subjects. We used a systematic approach to examine the diversity of the GAD65-specific T-cell repertoire in subjects with DRB1*04:01 haplotypes. Using class II tetramers, we observed responses to 15 GAD65 epitopes, including five novel epitopes. The majority were confirmed to be processed and presented. Upon stimulation with peptides, GAD-specific responses were equally broad in subjects with diabetes and healthy controls in the presence or absence of CD25(+) T cells, suggesting that a susceptible HLA is sufficient to generate a potentially autoreactive repertoire. Without depleting CD25(+) cells, GAD(113-132) and GAD(265-284) responses were significantly stronger in subjects with diabetes. Although nearly every individual responded to at least one GAD65 epitope, most were seen in less than half of the subjects tested, suggesting that multiple epitopes are recommended for immune monitoring.
Affiliations:Benaroya Research Institute at Virginia Mason, Seattle, WA, USA.
Reference Type:Literature
PubMed ID:23228173
Journal Volume:138
Article Pages:269-79
Journal ISSN:0019-2805
Article Chemical List:gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@51785e0;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@4b5637bc;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@9653e48;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@55dbedc9;gov.nih.nlm.ncbi.www.jaxb.impl.NameOfSubstanceImpl@59d85328
Article MeSH List:Amino Acid Sequence; CD4-Positive T-Lymphocytes(immunology); Case-Control Studies; Cell Line; Diabetes Mellitus, Type 1(genetics; immunology); Epitope Mapping; Epitopes, T-Lymphocyte(chemistry; immunology); Glutamate Decarboxylase(chemistry; immunology); HLA-DR Antigens(immunology); Humans; Interleukin-2 Receptor alpha Subunit(immunology; metabolism); Lymphocyte Depletion; Molecular Sequence Data
Curation Last Updated:2015-01-18 20:24:13