Human anti-asparaginyl-tRNA synthetase autoantibodies (anti-KS) increase the affinity of the enzyme for its tRNA substrate.
Autoantibodies directed against specific human aminoacyl-tRNA synthetases have been associated with a clinical picture including myositis, arthritis, interstitial lung disease and other features that has been referred to as the "anti-synthetase syndrome". Anti-asparaginyl-tRNA synthetase autoantibodies (anti-KS), the most recently described anti-synthetase autoantibodies, are directed against human cytosolic asparaginyl-tRNA synthetase and neutralize specifically its activity. Here we show that these antibodies recognize two epitopes on the human enzyme, an N-terminal epitope reactive in immunoblot experiments and a heat-labile epitope in the catalytic domain. In contrast to the well studied anti-Jo-1 autoantibodies anti-KS when bound to the synthetase increase the affinity of the synthetase for its tRNA substrate and prevent aminoacylation without interfering with the amino acid activation step.
Beaulande
M
M
EMBL, Grenoble Outstation, P.O. Box 156, F-38042 Grenoble Cedex 9, France.
Kron
M
M
Hirakata
M
M
Härtlein
M
M
D000215:Acylation / Q000187:drug effects; D000604:Amino Acyl-tRNA Synthetases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology* / Q000378:metabolism*; D000918:Antibody Specificity / Q000276:immunology; D001226:Aspartate-tRNA Ligase; D001323:Autoantibodies / Q000276:immunology* / Q000494:pharmacology; D001667:Binding, Competitive; D020134:Catalytic Domain; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D006801:Humans; D007106:Immune Sera / Q000276:immunology / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D009500:Neutralization Tests; D012346:RNA, Transfer, Amino Acyl; D012349:RNA, Transfer, Asp / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism
D001323:Autoantibodies; D000939:Epitopes; D007106:Immune Sera; D012346:RNA, Transfer, Amino Acyl; D012349:RNA, Transfer, Asp; D011994:Recombinant Proteins; D000604:Amino Acyl-tRNA Synthetases; D001226:Aspartate-tRNA Ligase; C029194:asparaginyl-tRNA synthetase