Isolation of potent human Fab fragments against a novel highly immunogenic region on human muscle acetylcholine receptor which protect the receptor from myasthenic autoantibodies

European Journal of Immunology

Volumn 35, Issue 2, 2005, Pages 632-643

  Fostieri, Efrosini ^a   Tzartos, Socrates J ^a,b   Berrih Aknin, Sonia ^c   Beeson, David ^d   Mamalaki, Avgi ^a  

^a HELLENIC PASTEUR INSTITUTE   (Greece)

^b UNIVERSITY OF PATRAS   (Greece)

^c CENTRE CHIRURGICAL MARIE LANNELONGUE   (France)

^d JOHN RADCLIFFE HOSPITAL   (United Kingdom)

Author keywords

Antigen binding fragment; Autoantibody; Human acetylcholine receptor; Myasthenia gravis

Indexed keywords

AUTOANTIBODY; CHOLINERGIC RECEPTOR; IMMUNOGLOBULIN F(AB) FRAGMENT; IMMUNOGLOBULIN HEAVY CHAIN; IMMUNOGLOBULIN LIGHT CHAIN; MONOCLONAL ANTIBODY; RECEPTOR SUBUNIT;

ADULT; ALPHA CHAIN; ANIMAL CELL; ARTICLE; B LYMPHOCYTE; BINDING AFFINITY; BINDING COMPETITION; CELL CULTURE; CELL SURFACE; CONTROLLED STUDY; DRUG ISOLATION; DRUG POTENCY; DRUG RECEPTOR BINDING; FEMALE; GENE CONSTRUCT; GENE LIBRARY; HUMAN; HUMAN CELL; IMMUNOGENICITY; IMMUNOMODULATION; IN VIVO STUDY; MOUSE; MUSCLE; MYASTHENIA GRAVIS; NONHUMAN; NUCLEOTIDE SEQUENCE; PHAGE DISPLAY; PRIORITY JOURNAL; PROTECTION; RAT; SOMATIC HYPERMUTATION; THYMUS;

AMINO ACID SEQUENCE; AUTOANTIBODIES; BASE SEQUENCE; EPITOPES; HUMANS; IMMUNOGLOBULIN FAB FRAGMENTS; MOLECULAR SEQUENCE DATA; MUSCLES; MYASTHENIA GRAVIS; PROTEIN STRUCTURE, TERTIARY; RECEPTORS, NICOTINIC;

EID: 14744297793     PISSN: 00142980     EISSN: None     Source Type: Journal    
DOI: 10.1002/eji.200425671     Document Type: Article

References (28)

1. Mishina, M., Takai, T., Imoto, K., Noda, M., Takahashi, T., Numa, S., Methfessel, C. and Sakmann, B., Molecular distinction between fetal and adult forms of muscle acetylcholine receptor. Nature 1986. 321: 406-411.
2. Richman, D. P., Wollmann, R. L., Maselli, R. A., Gomez, C. M., Corey, A. L., Agius, M. A. and Fairclough, R. H., Effector mechanisms of myasthenic antibodies. Ann. NY Acad. Sci. 1993. 681: 264-273.
3. Vincent, A., Palace, J. and Hilton-Jones, D., Myasthenia gravis. Lancet 2001. 357: 2122-2128.
4. Tzartos, S. J., Barkas, T., Cung, M. T., Mamalaki, A., Marraud, M., Orlewski, P., Papanastasiou, D., Sakarellos, C., Sakarellos-Daitsiotis, M., Tsantili, P. and Tsikaris, V., Anatomy of the antigenic structure of a large membrane autoantigen, the muscle-type nicotinic acetylcholine receptor. Immunol. Rev. 1998. 163: 89-120.
5. Heidenreich, F., Vincent, A., Willcox, N. and Newsom-Davis, J., Anti-acetylcholine receptor antibody specificities in serum and in thymic cell culture supernatants from myasthenia gravis patients. Neurology 1988. 38: 1784-1788.
6. Sims, G. P., Shiono, H., Willcox, N. and Stott, D. I., Somatic hypermutation and selection of B cells in thymic germinal centers responding to acetylcholine receptor in myasthenia gravis. J. Immunol. 2001. 167: 1935-1944.
7. Graus, Y. F., de Baets, M. H., Parren, P. W., Berrih-Aknin, S., Wokke, J., van Breda Vriesman, P. J. and Burton, D. R., Human anti-nicotinic acetylcholine receptor recombinant Fab fragments isolated from thymus-derived phage display libraries from myasthenia gravis patients reflect predominant specificities in serum and block the action of pathogenic serum antibodies. J. Immunol. 1997. 158: 1919-1929.
8. Mamalaki, A., Trakas, N. and Tzartos, S. J., Bacterial expression of a single-chain Fv fragment which efficiently protects the acetylcholine receptor against antigenic modulation caused by myasthenic antibodies. Eur. J. Immunol. 1993. 23: 1839-1845.
9. Papanastasiou, D., Poulas, K., Kokla, A. and Tzartos, S. J., Prevention of passively transferred experimental autoimmune myasthenia gravis by Fab fragments of monoclonal antibodies directed against the main immunogenic region of the acetylcholine receptor. J. Neuroimmunol. 2000. 104: 124-132.
10. Psaridi-Linardaki, L., Mamalaki, A., Remoundos, M. and Tzartos, S. J., Expression of soluble ligand- and antibody-binding extracellular domain of human muscle acetylcholine receptor alpha subunit in yeast Pichia pastoris. Role of glycosylation in alpha-bungarotoxin binding. J. Biol. Chem. 2002. 277: 26980-26986.
11. Tzartos, S., Langeberg, L., Hochschwender, S. and Lindstrom, J., Demonstration of a main immunogenic region on acetylcholine receptors from human muscle using monoclonal antibodies to human receptor. FEBS Lett. 1983. 158: 116-118.
12. Farrar, J., Portolano, S., Willcox, N., Vincent, A., Jacobson, L., Newsom-Davis, J., Rapoport, B. and McLachlan, S. M., Diverse Fab specific for acetylcholine receptor epitopes from a myasthenia gravis thymus combinatorial library. Int. Immunol. 1997. 9: 1311-1318.
13. Cardona, A., Pritsch, O., Dumas, G., Bach, J. F. and Dighiero, G., Evidence for an antigen-driven selection process in human autoantibodies against acetylcholine receptor. Mol. Immunol. 1995. 32: 1215-1223.
14. Fostieri, E., Beeson, D. and Tzartos, S. J., The conformation of the main immunogenic region on the alpha-subunit of muscle acetylcholine receptor is affected by neighboring receptor subunits. FEBS Lett. 2000. 481: 127-130.
15. Kordossi, A. A. and Tzartos, S. J., Monoclonal antibodies against the main immunogenic region of the acetylcholine receptor. Mapping on the intact molecule. J. Neuroimmunol. 1989. 23: 35-40.
16. Tzartos, S. J., Seybold, M. E. and Lindstrom, J. M., Specificities of antibodies to acetylcholine receptors in sera from myasthenia gravis patients measured by monoclonal antibodies. Proc. Natl. Acad. Sci. USA 1982. 79: 188-192.
17. Trakas, N. and Tzartos, S. J., Conjugation of acetylcholine receptor-protecting Fab fragments with polyethylene glycol results in a prolonged half-life in the circulation and reduced immunogenicity. J. Neuroimmunol. 2001. 120: 42-49.
18. Stassen, M. H., Machiels, B. M., Fostieri, E., Tzartos, S. J., Berrih-Aknin, S., Bosmans, E., Parren, P. W. and De Baets, M. H., Characterization of a fully human IgG1 reconstructed from an anti-AChR Fab. Ann. NY Acad. Sci. 2003. 998: 399-400.
19. Luther, M. A., Schoepfer, R., Whiting, P., Casey, B., Blatt, Y., Montal, M. S., Montal, M. and Linstrom, J., A muscle acetylcholine receptor is expressed in the human cerebellar medulloblastoma cell line TE671. J. Neurosci. 1989. 9: 1082-1096.
20. Beeson, D., Amar, M., Bermudez, I., Vincent, A. and Newsom-Davis, J., Stable functional expression of the adult subtype of human muscle acetylcholine receptor following transfection of the human rhabdomyosarcoma cell line TE671 with cDNA encoding the epsilon subunit. Neurosci. Lett. 1996. 207: 57-60.
21. Loutrari, H., Kokla, A., Trakas, N. and Tzartos, S. J., Expression of human-Torpedo hybrid acetylcholine receptor (AChR) for analysing the subunit specificity of antibodies in sera from patients with myasthenia gravis (MG). Clin. Exp. Immunol. 1997. 109: 538-546.
22. Lindstrom, J., Einarson, B. and Tzartos, S., Production and assay of antibodies to acetylcholine receptors. Methods Enzymol. 1981. 74 Pt C: 432-460.
23. Tzartos, S. J., Rand, D. E., Einarson, B. L. and Lindstrom, J. M., Mapping of surface structures of electrophorus acetylcholine receptor using monoclonal antibodies. J. Biol. Chem. 1981. 256: 8635-8645.
24. Tzartos, S., Langeberg, L., Hochschwender, S., Swanson, L. W. and Lindstrom, J., Characteristics of monoclonal antibodies to denatured Torpedo and to native calf acetylcholine receptors: species, subunit and region specificity. J. Neuroimmunol. 1986. 10: 235-253.
25. Barbas, C. F. and Burton, D. R., Monoclonal antibodies from combinatorial libraries (1994 Cold Spring Harbor Laboratory Course). Cold Spring Harbor 1994.
26. Barbas, C. F., 3rd, Kang, A. S., Lerner, R. A. and Benkovic, S. J., Assembly of combinatorial antibody libraries on phage surfaces: the gene III site. Proc. Natl. Acad. Sci. USA 1991. 88: 7978-7982.
27. Byun, C. H., Park, J. Y., Akamizu, T. and Chae, C. B., Identification of the peptides that inhibit the function of human monoclonal thyroid-stimulating antibodies from phage-displayed peptide library. J. Clin. Endocrinol. Metab. 2001. 86: 3311-3318.
28. Kabat, E. A., Wu, T. T., Perry, H. M., Gottesman, K. S. and Foeller, C., Sequences of Proteins of Immunological Interest, National Institutes of Health, Bethesda, MD 1991.