Monoclonal antibody 76F distinguishes IA-2 from IA-2β and overlaps an autoantibody epitope

Piquer, Sandra, Valera, Lionel, Lampasona, Vito , Jardin-Watelet, Benedicte, Roche, Stephanie, Granier, Claude, Roquet, Francoise, Christie, Michael R., Giordano, Tiziana, Malosio, Maria-Luisa, Bonifacio, Ezio and Laune, Daniel (2006) Monoclonal antibody 76F distinguishes IA-2 from IA-2β and overlaps an autoantibody epitope. Journal of Autoimmunity, 26 (3). pp. 215-222. ISSN 0896-8411

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Monoclonal antibody 76F distinguishes IA-2 from IA-2β and overlaps an autoantibody epitope

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IA-2 and IA-2β are highly related proteins that are autoantigens in type 1 diabetes, and provide a model for developing reagents and assays that distinguish similar proteins with unique autoantibody epitopes.

Monoclonal antibodies (mAb) to IA-2 and IA-2β were prepared and tested for their ability to bind to the related proteins and their ability to compete for specific autoantibody epitope binding by sera from patients with type 1 diabetes.

Monoclonal antibodies that specifically bound IA-2 (76F) or bound both IA-2 and IA-2β (A9) were isolated and characterized. 76F mAb recognized IA-2 of human, rat and mouse origin in native and denatured forms and had an epitope specificity for residues 626–630 (FEYQD) which are found in the juxtamembrane (JM) region of human and mouse IA-2, but not IA-2β. This region overlaps with the autoantibody epitope JM2. Binding to the 76F monoclonal antibody was specifically inhibited by sera with antibodies to the JM2 epitope but not with antibodies to the adjacent JM1 epitope, indicating that unique epitopes can be distinguished by this approach.

76F mAb has the unique property to distinguish between the two closely related autoantigens IA-2 and IA-2β by targeting an IA-2 specific epitope of the juxtamembrane region. The findings define an approach to develop assays for specific antibody epitope measurements which may be relevant for disease prognosis and monitoring intervention therapies.

Keywords:autoantibody, autoantigen, IA 2 antigen, IA 2beta antigen, Ia antigen, monoclonal antibody, monoclonal antibody 76F, unclassified drug, animal cell, animal experiment, animal tissue, antigen binding, article, controlled study, epitope mapping, human, human cell, male, mouse, nonhuman, priority journal, prognosis, protein analysis, protein expression, rat, Amino Acid Sequence, Animals, Antibodies, Monoclonal, Antibody Specificity, Autoantibodies, Autoantigens, Diabetes Mellitus, Type 1, Epitopes, Immunohistochemistry, Immunoprecipitation, Membrane Proteins, Mice, Mice, Inbred BALB C, Molecular Sequence Data, Protein-Tyrosine-Phosphatase
Subjects:A Medicine and Dentistry > A100 Pre-clinical Medicine
Divisions:College of Science > School of Life Sciences
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ID Code:18125
Deposited On:05 Aug 2015 15:09

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