High Affinity Presentation of an Autoantigenic Peptide in Type I Diabetes by an HLA Class II Protein Encoded in a Haplotype Protecting From Disease
| Autor: | Günther Jung, Peter van Endert, Gerald T. Nepom, Hélène Cohen, Christian Boitard, Heike Otto, José Timsit, Jean Marie Bach |
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| Rok vydání: | 1997 |
| Předmět: |
Adult
Male endocrine system diseases Molecular Sequence Data Immunology Antigen presentation Peptide binding Human leukocyte antigen Biology Autoantigens Epitope Cell Line Antigen immune system diseases Humans Immunology and Allergy Amino Acid Sequence Peptide sequence Genetics Antigen Presentation Polymorphism Genetic Glutamate Decarboxylase Histocompatibility Antigens Class II nutritional and metabolic diseases HLA-DR Antigens Middle Aged Histocompatibility Diabetes Mellitus Type 1 Epitope mapping Haplotypes Peptides Epitope Mapping Protein Binding T-Lymphocytes Cytotoxic |
| Zdroj: | Journal of Autoimmunity. 10:375-386 |
| ISSN: | 0896-8411 |
| DOI: | 10.1006/jaut.1997.0143 |
| Popis: | Polymorphism of the genes coding for the human histocompatibility leukocyte antigen class II DR and DQ molecules makes the single largest genetic contribution to the risk of developing insulin-dependent diabetes mellitus (IDDM) and can be associated with highly elevated as well as decreased disease frequency. The mechanism of IDDM risk modification by HLA polymorphism is likely to involve differential presentation of autoantigenic peptides by HLA class II proteins. We have generated T cell lines (TCL) with specificity for the IDDM autoantigen 65 kDa glutamic acid decarboxylase (GAD65) from lymphocytes of two patients carrying HLA class II alleles associated with distinct risk of IDDM (DRB1*0101/0401 and 1302/1501). For both patients, TCL generated at various time points all recognized single epitopes mapped as GAD 88-99 and 248-257, respectively. These epitopes are presented by the DRB1*0101 and DRB5*0101, HLA class II molecules associated with a moderately elevated risk of IDDM, or carried in a strongly protective haplotype, respectively. In an HLA/peptide binding assay, epitope GAD 248-257 was shown to possess high affinity for DRB5*0101. This epitope overlaps with a central GAD peptide binding to the high risk allele DQB1*0302 and containing a Coxsackie P2C-identical mimicry sequence, raising the possibility of competition of DRB5*0101 and DQB1*0302 for binding of a central GAD65 fragment. |
| Databáze: | OpenAIRE |
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