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.
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References
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).
D.C. Benjamin, Molecular Approaches to the Study of B-cell Epitopes. Intern. Rev. Immunol. 7:149 (1991).
D.C. Benjamin and S.S. Perdue, Techniques for Determining Epitopes for Antibodies and T-Cell Receptors. Ann. Rev. Medicinal Chem. 27:189 (1993).
E.D. Getzoff, J.A. Tainer, and RA Lerner, The Chemistry and Mechanism of Antibody Binding to Protein Antigens. Adv. Immunol. 43:1 (1988).
J.A. Berzofsky, Intrinsic and Extrinsic Factors in Protein Antigenic Structure. Science. 229:932 (1985).
D.R. Davies, S. Sheriff, and E.A. Padlan. Antibody-Antigen Complexes, J. Biol. Chem. 263:10541 (1988).
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).
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).
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).
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).
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).
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).
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).
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).
S. Sheriff, Some Methods for Examining the Interactions between Two Molecules. Immunomethods 3:191 (1993).
M.L. Connolly, Analytical Molecular Surface Calculation. J. Appl. Crystallography. 16:548 (1983).
D.J. Barlow, M.S. Edwards, and J.M. Thornton, Continuous and Discontinuous Protein Antigenic Determinants. Nature 322:747 (1986).
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).
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).
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).
L. Jin, B.M. Fendly, and J.A. Wells, High Resolution Functional Analysis of Antibody-Antigen Interactions. J. Mol. Biol. 226:851 (1992).
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).
J. Novotny, Protein Antigenicity:A Thermodynamic Approach. Mol. Immunol. 28:201 (1991).
T.P. Hopp and K.R. Woods, Prediction of Protein Antigenic Determinants from Amino Acid Sequences. Proc. Nat. Acad. Sci. USA. 78:3824 (1981).
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).
E. Westhof, Correlation of Segmental Mobility and the Location of Antigenic Determinants in Proteins. Nature 311:123 (1984).
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).
B.D. Spangler, Binding To Native Proteins by Antipeptide Monoclonal Antibodies. J. Immunol. 146:1591 (1991).
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).
S.J. Smith-Gill, Protein Epitopes:Functional and Structural Differences. Res. in Immunology. In press (1994).
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© 1995 Plenum Press, New York
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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
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DOI: https://doi.org/10.1007/978-1-4613-0331-2_8
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