Immunogenic HLA-DR-Presented Self-Peptides Identified Directly from Clinical Samples of Synovial Tissue, Synovial Fluid, or Peripheral Blood in Patients with Rheumatoid Arthritis or Lyme Arthritis
| Autor: | Catherine E. Costello, Yu Huang, Jiyang Zhang, Elise E. Drouin, Chunxiang Yao, Allen C. Steere, Deborah R. Leon, Qi Wang |
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| Rok vydání: | 2016 |
| Předmět: |
Adult
0301 basic medicine Adolescent T-Lymphocytes Gene Expression Arthritis Lyme Arthritis Autoantigens Biochemistry Peripheral blood mononuclear cell Article Arthritis Rheumatoid 03 medical and health sciences Immune system Synovial Fluid medicine HLA-DR Humans Synovial fluid Aged Antigen Presentation B-Lymphocytes Lyme Disease business.industry Synovial Membrane Molecular Sequence Annotation HLA-DR Antigens General Chemistry Middle Aged medicine.disease Gene Ontology 030104 developmental biology medicine.anatomical_structure Rheumatoid arthritis Immunology Synovial membrane Peptides business |
| Zdroj: | Journal of Proteome Research. 16:122-136 |
| ISSN: | 1535-3907 1535-3893 |
| Popis: | HLA-DR-molecules are highly expressed in synovial tissue (ST), the target of the immune response in chronic inflammatory forms of arthritis. Here, we used LC-MS/MS to identify HLA-DR-presented self-peptides in cells taken directly from clinical samples: ST, synovial fluid mononuclear cells (SFMC), or peripheral blood mononuclear cells (PBMC) from five patients with rheumatoid arthritis (RA) and eight with Lyme arthritis (LA). We identified 1,593 non-redundant HLA-DR-presented peptides, derived from 870 source proteins. Sixty-seven percent of the peptides identified in SFMC and 55% of those found in PBMC were found in ST, but analysis of SFMC/PBMC also revealed new antigen-presented peptides. Peptides were synthesized and examined for reactivity with the patients’ PBMC. To date, three autoantigens in RA and four novel autoantigens in LA, presented in ST and/or PBMC, were shown to be targets of T- and B-cell responses in these diseases; ongoing analyses may add to this list. Thus, immunoprecipitation and LC-MS/MS can now identify hundreds of HLA-DR-presented self-peptides from individual patients’ tissues or fluids with mixed cell populations. Importantly, identification of HLA-DR-presented peptides from SFMC or PBMC allows testing of more patients, including those early in the disease. Direct analysis of clinical samples facilitates identification of novel immunogenic T-cell epitopes. Data are available via ProteomeXchange (identifier PXD003051). |
| Databáze: | OpenAIRE |
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