Skip to main content

B-cell epitopes:Fact and fiction

  • Chapter
Book cover Inhibitors to Coagulation Factors

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 386))

Abstract

Antibodies are present as integral membrane receptors on cells of the B lymphocyte lineage and as proteins secreted by members of this cell family. As such they represent one of several macromolecular complexes used by the immune system in the specific recognition of antigenic molecules. In addition to antibody these include T-cell receptors and the class I and class II molecules encoded by genes within the major histocompatibility complex (MHC). In humans, antibodies are produced in response to foreign particles such as infectious organisms, transplantation antigens and, in genetically deficient individuals, to human or animal proteins provided as therapeutic agents in the treatment of certain diseases. Of particular interest at this symposium are antibodies produced to coagulation factors and the nature of the epitopes on these factors. It has become increasingly apparent that a significant fraction of patients when provided with the factor, isolated either from natural sources or from recombinant material, respond by producing antibody that inhibits the function of that factor. In order to fully understand the mechanisms of the production of these antibody inhibitors to coagulation factors and to have a hope of successfully treating these individuals, one must have a better understanding of the nature of the antigenic sites on the factors to which the immune response is directed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. D.C. Benjamin, J.A. Berzofsky, IJ. East, F.R.N. Gurd, C. Hanmim, SJ. Leach, E. Margoliash, J.G. Michael, A. Miller, E.M. Prager, M. Reichlin, E.E. Sercarz, SJ. Smith-Gill, P.E. Todd, and A.C. Wilson, The Antigenic Structure of Proteins:A Reappraisal. Ann. Rev. Immunol. 2:67 (1984).

    Article  CAS  Google Scholar 

  2. D.C. Benjamin, Molecular Approaches to the Study of B-cell Epitopes. Intern. Rev. Immunol. 7:149 (1991).

    Article  CAS  Google Scholar 

  3. D.C. Benjamin and S.S. Perdue, Techniques for Determining Epitopes for Antibodies and T-Cell Receptors. Ann. Rev. Medicinal Chem. 27:189 (1993).

    Article  Google Scholar 

  4. E.D. Getzoff, J.A. Tainer, and RA Lerner, The Chemistry and Mechanism of Antibody Binding to Protein Antigens. Adv. Immunol. 43:1 (1988).

    Article  CAS  Google Scholar 

  5. J.A. Berzofsky, Intrinsic and Extrinsic Factors in Protein Antigenic Structure. Science. 229:932 (1985).

    Article  PubMed  CAS  Google Scholar 

  6. D.R. Davies, S. Sheriff, and E.A. Padlan. Antibody-Antigen Complexes, J. Biol. Chem. 263:10541 (1988).

    PubMed  CAS  Google Scholar 

  7. A.G. Amit, RA. Mariuzza, S.E.V. Phillips, and RJ. Poljak, Three-Dimensional Structure of an Antigen-Antibody Complex at 2.8 A Resolution. Science. 233:747. (1986).

    Article  PubMed  CAS  Google Scholar 

  8. J.N. Herron, X.M. He, M.L. Mason, E.W. Voss, Jr., and A.B. Edmunson, Three-Dimensional Structure of a Fluorescein-Fab Complex Crystallized in 2-Methyl-2,4-Pentanediol. Proteins 5:271 (1989).

    Article  PubMed  CAS  Google Scholar 

  9. P.D. Jeffrey, R.K. Strong, L.C. Sieker, C.Y.Y. Chang, R.L. Campbell, G.A. Petsko, E. Haber, M.N. Margolies, and S. Sheriff, 26–10 Fab-Digoxin Complex:Affinity and Specificity Due to Surface Complementarity. Proc. Nat. Acad. Sci. USA 90:10310 (1993).

    Article  PubMed  CAS  Google Scholar 

  10. R.L. Stanfield, TM. Fieser, RA. Lerner, and I.A. Wilson, Crystal Structures of an Antibody to a Peptide and Its Complex with Peptide Antigen at 2.8 Angstroms. Science 248:712 (1992).

    Article  Google Scholar 

  11. J.M. Rini, U. Schulze-Gahmen, and I.A. Wilson, Structural Evidence for Induced Fit as a Mechanism for Antigen-Antibody Recognition. Science 255:959 (1992).

    Article  PubMed  CAS  Google Scholar 

  12. S. Sheriff, E.W. Silverton, E.A. Padlan, G.H. Cohen, S.J. Smith-Gill, B.C. Finzel, and D.R. Davies. Three-Dimensional Structure of an Antibody-Antigen Complex. Proc. Nat. Acad. Sci. USA. 84:8075 (1987).

    Article  PubMed  CAS  Google Scholar 

  13. E.A. Padlan, E.W. Silverton, S. Sheriff, G.H. Cohen, SJ. Smith-Gill, and D.R. Davies, Structure of an Antibody-Antigen Complex:Crystal Structure of the HyHEL-10 Fab-Lysozyme Complex. Proc. Nat. Acad. Sci. USA. 86:5938 (1989).

    Article  PubMed  CAS  Google Scholar 

  14. P.M. Colman, W.G. Laver, J.N. Varghese, A.T. Baker, P.A. Tulloch, G.M. Air, and R.G. Webster, Three-Dimensional Structure of a Complex of Antibody with Influenza Virus Neuraminidase. Nature 326:358 (1987).

    Article  PubMed  CAS  Google Scholar 

  15. S. Sheriff, Some Methods for Examining the Interactions between Two Molecules. Immunomethods 3:191 (1993).

    Article  CAS  Google Scholar 

  16. M.L. Connolly, Analytical Molecular Surface Calculation. J. Appl. Crystallography. 16:548 (1983).

    Article  CAS  Google Scholar 

  17. D.J. Barlow, M.S. Edwards, and J.M. Thornton, Continuous and Discontinuous Protein Antigenic Determinants. Nature 322:747 (1986).

    Article  PubMed  CAS  Google Scholar 

  18. S.J. Smith-Gill, T.B. Lavoie, and CR. Mainhart, Antigenic Regions Defined by Monoclonal Antibodies Correspond to Structural Domains of Avian Lysozyme. J. Immunol. 133:384 (1984).

    PubMed  CAS  Google Scholar 

  19. J. Novotny, R.E. Bruccoleri, and FA. Saul., On the Attribution of Binding Energy in Antigen-Antibody Complexes McPC 603, D1.3 and HyHEL-5. Biochemistry 28:4735 (1989).

    Article  PubMed  CAS  Google Scholar 

  20. A.M. Smith and D.C. Benjamin, The Antigenic Surface of Staphylococcal Nuclease. II. Analysis of the N-l Epitope by Site-Directed Mutagenesis. J. Immunol 146:1259 (1991).

    PubMed  CAS  Google Scholar 

  21. L. Jin, B.M. Fendly, and J.A. Wells, High Resolution Functional Analysis of Antibody-Antigen Interactions. J. Mol. Biol. 226:851 (1992).

    Article  PubMed  CAS  Google Scholar 

  22. L. Prasad, S. Sharma, M. Fandonselaar, J.W. Quail, J.S. Lee, E.B. Waygood, K. Wilson, Z. Dauter, and L.T.J. Delbaere, Mutagenesis for Epitope Mapping:Structure of an Antibody-Protein Antigen Complex. J. Biol. Chem. 268:10705 (1993).

    PubMed  CAS  Google Scholar 

  23. J. Novotny, Protein Antigenicity:A Thermodynamic Approach. Mol. Immunol. 28:201 (1991).

    CAS  Google Scholar 

  24. T.P. Hopp and K.R. Woods, Prediction of Protein Antigenic Determinants from Amino Acid Sequences. Proc. Nat. Acad. Sci. USA. 78:3824 (1981).

    Article  PubMed  CAS  Google Scholar 

  25. J. Novotny, M. Handschumacher, E. Haber, R.E. Bruccoleri, W.B. Carlson, E.W. Fanning, J.A. Smith, and CD. Rose, Antigenic Determinants in Proteins Coincide with Surface Regions Accessible to Large Probes (Antibody Domains). Proc. Nat. Acad. Sci. USA. 83:226 (1986).

    Article  PubMed  CAS  Google Scholar 

  26. E. Westhof, Correlation of Segmental Mobility and the Location of Antigenic Determinants in Proteins. Nature 311:123 (1984).

    Article  PubMed  CAS  Google Scholar 

  27. M.H.V. Van Regenmortel, J.P. Briand, Z. Al Moudallal, D. Altschuh, and E. Westhof, in:“Current Communications in Molecular Biology:Immune Recognition of Protein Antigens,” WG. Laver and G.M. Air, Eds., Cold Spring Harbor Press, Cold Spring Harbor, N.Y. (1985).

    Google Scholar 

  28. B.D. Spangler, Binding To Native Proteins by Antipeptide Monoclonal Antibodies. J. Immunol. 146:1591 (1991).

    PubMed  CAS  Google Scholar 

  29. T.M. Fieser, J.A. Tainer, H.M. Geysen, R.A. Houghton, and RA. Lerner, Influence of Protein Flexibility and Peptide Conformation on Reactivity of Monoclonal AntiPeptide A antibodies with a Protein a- helix. Proc. Nat. Acad. Sci. USA. 84:8568 (1987).

    Article  PubMed  CAS  Google Scholar 

  30. S.J. Smith-Gill, Protein Epitopes:Functional and Structural Differences. Res. in Immunology. In press (1994).

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Plenum Press, New York

About this chapter

Cite this chapter

Benjamin, D.C. (1995). B-cell epitopes:Fact and fiction. In: Aledort, L.M., Hoyer, L.W., Lusher, J.M., Reisner, H.M., White, G.C. (eds) Inhibitors to Coagulation Factors. Advances in Experimental Medicine and Biology, vol 386. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-0331-2_8

Download citation

  • DOI: https://doi.org/10.1007/978-1-4613-0331-2_8

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-8001-6

  • Online ISBN: 978-1-4613-0331-2

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics