Advertisement

Epitope Mapping of TTR (Prealbumin) and TTR(Met30) with Monoclonal Antibodies

  • Paulo M. P. Costa
  • Maria João M. Saraiva
  • Björn Jakobsson
  • Peter Biberfeld
  • V. Peter Collins
  • Pedro P. Costa
Chapter

Abstract

Familial Amyloidotic Polyneuropathy, type I, is an inherited autossomal dominant disease in which an abnormal TTR with a methionine for valine substitution at position 30 (TTR(Met30)) was demonstrated1,2, both in the amyloid fibrils and in patients serum. However, it does not differ from normal TTR in most physicochemical properties studied3, including the electrophoretic mobility and ligand affinities, thus making detection and purification difficult. A significative improvement in this situation would be achieved if a monoclonal antibody (mab) selective for the abnormal protein could be developed. A likely requirement for such a mab is that it recognizes an epitope that includes the mutation point, so the mabs we have so far obtained were tested against peptides derived from TTR by tryptic digestion and CNBr cleavage, in an attempt to define those epitopes.

Keywords

Amyloid Fibril Tryptic Digestion Myeloma Cell Line Ligand Affinity Karolinska Hospital 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    M. J. M. Saraiva, P. P. Costa, S. Birken, and Goodman, D. S., Presence of an abnormal transthyretin (prealbumin) in Portuguese patients with familial amyloidotic polyneuropathy, Trans. Ass. Amer. Phys., 96: 261 (1983).Google Scholar
  2. 2.
    S. Tawara, M. Nakazato, K. Kangawa, H. Matsuo, and S. Araki, Identification of amyloid prealbumin variant in familial amyloidotic polyneuropathy (Japanese type), Biochem. Biophys. Res. Commun., 116: 880 (1983).CrossRefGoogle Scholar
  3. 3.
    M. J. M. Saraiva, P. P. Costa, and D. S. Goodman, Studies on plasma trans-thyretin (prealbumin) in familial amyloidotic polyneuropathy, Portuguese type, J. Lab. Clin. Med., 102: 590 (1983).Google Scholar
  4. 4.
    J. W. Goding, Antibody production by hybridomas, J. Immunol. Meth., 39: 285 (1980).CrossRefGoogle Scholar
  5. 5.
    M. J. M. Saraiva, P. P. Costa, and D. S. Goodman, Biochemical marker in familial amyloidotic polyneuropathy, Portuguese type, J. Clin. Invest., 76: 2171 (1985).CrossRefGoogle Scholar
  6. 6.
    M. J. M. Saraiva, S. Birken, P. P. Costa, and D. S. Goodman, Amyloid fibril protein in familial amyloidotic polyneuropathy, Portuguese type. Definition of molecular abnormality in transthyretin (prealbumin), J. Clin. Invest., 74: 104 (1984).CrossRefGoogle Scholar
  7. 7.
    Y. Kanda, D. S. Goodman, R. E. Canfield, and F. J. Morgan, The aminoacid sequence of human plasma prealbumin, J. Biol. Chem., 249: 6796 (1974).Google Scholar

Copyright information

© Springer Science+Business Media New York 1988

Authors and Affiliations

  • Paulo M. P. Costa
    • 1
  • Maria João M. Saraiva
    • 1
  • Björn Jakobsson
    • 2
  • Peter Biberfeld
    • 3
  • V. Peter Collins
    • 3
  • Pedro P. Costa
    • 1
  1. 1.Centro de Estudos de Paramiloidose (CEP)Instituto Nacional de SaúdePortoPortugal
  2. 2.Departments of Pathology and Clinical ChemistryDanderyd HospitalStockholmSweden
  3. 3.Department of PathologyKarolinska HospitalStockholmSweden

Personalised recommendations