Complexity of Human Immune Response Profiles for CD4+T Cell Epitopes from the Diabetes Autoantigen GAD65
| Autor: | Susan Masewicz, Niecey Meldrum, Lakshmi K. Gaur, Gerald T. Nepom, Lori Moriarity, Vivian H. Gersuk, William Hagopian |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
CD4-Positive T-Lymphocytes
T cell Molecular Sequence Data Immunology Epitopes T-Lymphocyte Major histocompatibility complex Autoantigens Epitope Immune system Antigen medicine Humans Immunology and Allergy Amino Acid Sequence Autoantibodies biology Glutamate Decarboxylase Antigen processing T-cell receptor HLA-DR Antigens T lymphocyte Molecular biology Isoenzymes Diabetes Mellitus Type 1 medicine.anatomical_structure biology.protein Cytokines |
| Zdroj: | Autoimmunity. 34:231-240 |
| ISSN: | 1607-842X 0891-6934 |
| Popis: | Complex protein antigens contain multiple potential T cell recognition epitopes, which are generated through a processing pathway involving partial antigen degradation via proteases, binding to MHC molecules, and display on the APC surface, followed by recognition via the T cell receptor. We have investigated recognition of the GAD65 protein, one of the well-characterized autoantigens in type I diabetes, among individuals carrying the HLA-DR4 haplotypes characteristic of susceptibility to IDDM. Using sets of 20-mer peptides spanning the GAD65 molecule, multiple immunostimulatory epitopes were identified, with diverse class II DR molecules functioning as the restriction element. The majority of T cell responses were restricted by DRB1 molecules; however, DRB4 restricted responses were also observed. Antigen-specific T cell clones and lines were derived from peripheral blood samples of pre-diabetic and IDDM patients and T cell recognition and response were measured. Highly variable proliferative and cytokine release profiles were observed, even among T cells specific for a single GAD65 epitope. |
| Databáze: | OpenAIRE |
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