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Identification of naturally processed T cell epitopes from glutamic acid decarboxylase presented in the context of HLA-DR alleles by T lymphocytes of recent onset IDDM patients.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Endl, Josef Otto, Hendrik Jung, Guenther Dreisbusch, B. Donié, Frédéric Stahl, Philip Elbracht, Rudi Schmitz, Gerd Meinl, Edgar Hummel, Michael Ziegler, Anette-G. Wank, Rudolf Schendel, Dolores J. |
| Copyright Year | 1997 |
| Abstract | Glutamic acid decarboxylase (GAD) has been defined as a major target antigen in insulin-dependent diabetes mellitus (IDDM). To identify the molecular ligands triggering a T cell response to GAD, a panel of human GAD65-specific T lymphocyte lines was generated from peripheral blood of three recent onset IDDM patients. All lines derived from a patient expressing the high-risk-conferring HLA-DR*0301/ *0401 haplotypes recognized a single epitope localized between amino acid positions 270 and 283 of GAD65, a stretch that is located in close proximity to the homology region shared with Coxsackie virus P2-C protein. All lines with this specificity were restricted to the DRA, B1*0401 product of the DR4 haplotype. Analysis of the GAD-specific T cell response in a second patient homozygous for DR4 haplotypes demonstrated that the same DRA, B1*0401 allele selected T cells specific for a different determinant. The T cell response profile in a third patient showed that DR*1501/ *1601-encoding haplotypes could present at least three different epitopes to GAD65-specific T lymphocytes. One of these epitopes was presented by a DR allele associated with the resistance-conferring DRB1*1501 haplotype. GAD-specific T cell lines could not be isolated from HLA class II-matched normal individuals. Our data reveal that (a) the T cell response to GAD65 is quite heterogenous in recent onset IDDM patients; (b) HLA-DR, not DQ, seems to be the principal restriction element used by T cells present at the onset of the disease; and (c) T cells responding to epitopes containing identical sequences to Coxsackie virus P2-C protein were not detected. |
| Starting Page | 23 |
| Ending Page | 30 |
| Page Count | 8 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://dm5migu4zj3pb.cloudfront.net/manuscripts/119000/119423/JCI97119423.pdf |
| PubMed reference number | 9153283v1 |
| Volume Number | 99 |
| Issue Number | 10 |
| Journal | The Journal of clinical investigation |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Alleles Amino Acids Carboxy-Lyases Cellular Phone Diabetes Mellitus Epitopes GAD1 gene GAD2 gene Generalized Anxiety Disorder Glutamate Decarboxylase Glutamic Acid HLA Antigens HLA-DR Antigens Haplotypes Helper-Inducer T-Lymphocyte Histocompatibility Antigens Class II Homologous Gene Homozygote Leukemia, B-Cell Ligands Murine sarcoma viruses Patients Peripheral Vascular Diseases SLC26A3 gene childhood lymphocyte depletion Hodgkin's lymphoma |
| Content Type | Text |
| Resource Type | Article |
