Sera from JRA patients contain antibodies against a defined epitope in chromosomal protein HMG-17.
Autoantibodies against the nonhistone nucleosomal protein HMG-17 have been detected in a high percentage of ANA-positive patients with pauciarticular-onset JRA4. Here we report on the epitope mapping of the HMG-17 autoantigen with a set of overlapping and nested synthetic peptides spanning the entire amino acid sequence of the human HMG-17 protein. Competition ELISA experiments defined a proline and lysine rich octapeptide PKPEPKPK as the major epitope recognized by more than 70% of the HMG-17 positive JRA sera. Point mutations introduced in the autoimmune peptide determined the amino acid residues important for autoantibody recognition. Computer based sequence comparison shows close homology between the HMG-17 autoimmune epitope and certain infectious organisms, supporting the possibility that molecular mimicry is an important factor in the etiology of JRA.
Neuer
G
G
Institute of Molecular Genetics, University of Heidelberg, Federal Republic of Germany.
Bautz
F A
FA
Bustin
M
M
Michels
H
H
Truckenbrodt
H
H
D000595:Amino Acid Sequence; D000974:Antibodies, Antinuclear / Q000276:immunology*; D000918:Antibody Specificity; D001171:Arthritis, Juvenile / Q000097:blood / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D001327:Autoimmune Diseases / Q000097:blood / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D006609:High Mobility Group Proteins / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000276:immunology; D017386:Sequence Homology, Amino Acid
D000974:Antibodies, Antinuclear; D001324:Autoantigens; D000939:Epitopes; D006609:High Mobility Group Proteins; D010446:Peptide Fragments