Juvenile arthritis, HLA-A2 and binding of DEK oncogene-peptides

• Published in: Human immunology 1998-07, Vol.59 (7), p.443-450
• Main Authors: Forero, Leonardo, Zwirner, Norberto W, Fink, Chester W, Fernández-Viña, Marcelo A, Stastny, Peter
• Format: Article
• Language: English
• Subjects: Arthritis, Juvenile - immunology; Arthritis, Juvenile - metabolism; Autoantigens - chemistry; Autoantigens - metabolism; Binding Sites - immunology; Chromosomal Proteins, Non-Histone; HLA-A2 Antigen - metabolism; Humans; Oligopeptides - metabolism; Oncogene Proteins - metabolism; Poly-ADP-Ribose Binding Proteins; Protein Binding - immunology
• ISSN: 0198-8859; 1879-1166
• DOI: 10.1016/S0198-8859(98)00034-2

Previous studies have shown that susceptibility to Pauciarticular Juvenile Arthritis is associated with HLA-A∗0201. Recently, autoantibodies against the protein of the DEK oncogene have been found in sera of patients with this disease. If T cells are involved in the pathogenesis of joint lesions, it is possible that they target autoantigens presented by HLA-A∗0201. Therefore, we investigated whether DEK-derived peptides can bind efficiently to HLA-A∗0201. Nonameric peptides selected considering anchor positions 2 and 9, and preferred amino acids at other positions, were incubated either with the human TAP-deficient cell line 174CEM.T2 (T2) or with the homozygous B cell line JESTHOM (A∗0201, B∗2705, Cw1), previously depleted of endogenous peptides. Binding was measured as the increase of detection of fully assembled, HLA-A∗0201 molecules by flow cytometry with the anti-HLA-A2 monoclonal antibody (mAb) BB7.2. Three out of ten selected DEK-derived peptides showed binding to HLA-A∗0201, which was peptide concentration-dependent (1 μM to 100 μM). DEK155-163 (AMLKSICEV), which also has two preferred amino acid residues at positions 6 and 8, yielded the highest binding. DEK163-171 (VLDLERSGV) and DEK72-80 (SLQREPFTI), which also has one preferred amino acid residue at position 8, also were able to bind to HLA-A∗0201. Furthermore, peptide-induced, fully assembled, HLA-A∗0201 molecules were immunoprecipitated with the BB7.2 mAb from metabolically-labeled T2 cells incubated with DEK72-80, DEK155-163, and DEK163-171. A faint band was observed in the immunoprecipitates of cells incubated with DEK65-73 (it carries a preferred amino acid residue at position 6), suggesting that this peptide interacts weakly with HLA-A∗0201. These results indicate that several nonameric peptides derived from the DEK protein can bind to HLA-A∗0201 and suggest that the complexes formed may be able to stimulate CD8 + T cells in patients with Pauciarticular Juvenile Arthritis.