JUVENILE ARTHRITIS, HLA-A2 AND BINDING OF DEK ONCOGENE-PEPTIDES

Previous studies have shown that susceptibility to Pauciarticular Juve nile Arthritis is associated with HLA-A0201. Recently, autoantibodies against the protein of the DEK oncogene have been found in sera of pa tients with this disease. If T cells are involved in the pathogenesis of joint lesions, it is possible that they target autoantigens present ed by HLA-A0201. Therefore, we investigated whether DEK-derived pepti des can bind efficiently to HLA-A0201. Nonameric peptides selected co nsidering anchor positions 2 and 9, and preferred amino acids at other positions, were incubated either with the human TAP-deficient cell li ne 174CEM.T2 (T2) or with the homozygous B cell line JESTHOM (A0201, B2705, Cw1), previously depleted of endogenous peptides. Binding was measured as the increase of detection of fully assembled, HLA-A0201 m olecules by flow cytometry with the anti-HLA-A2 monoclonal antibody (m Ab) BB7.2. Three out of ten selected DEK-derived peptides showed bindi ng to HLA-A0201,which was peptide concentration-dependent (1 mu M to 100 mu M). DEK155-163 (AMLKSICEV), which also has two preferred amino acid residues at positions 6 and 8, yielded the highest binding. DEK16 3-171 (VLDLERSGV) and DEK72-80 (SLQREPFTI), which also has one preferr ed amino acid residue at position 8, also were able to bind to HLA-A0 201. Furthermore, peptide-induced, fully assembled, HLA-A0201 molecul es were immunoprecipitated with the BB7.2 mAb from metabolically-label ed T2 cells incubated with DEK72-80, DEK155-163, and DEK163-171. A fai nt band was observed in the immunoprecipitates of cells incubated with DEK65-73 tit carries a preferred amino acid residue at position 6), s uggesting that this peptide interacts weakly with HLA-A0201, These re sults indicate that several nonameric peptides derived from the DEK pr otein can bind to HLA-A0201 and suggest that the complexes formed may be able to stimulate CD8(+) T2 cells in patients with Pauciarticular Juvenile Arthritis. Human Immunology 59, 443-450 (1998). (C) American Society for Histocompatibility and Immunogenetics, 1998. Published by Elsevier Science Inc.