Complementarity, specificity and the nature of epitopes and paratopes in multivalent interactions.

Structural elements of an antibody (Ab) or antigen (Ag) distant from the actual sites mediating contact between Ab and Ag can exert substantial influence on binding to, and discrimination among, multivalent targets. Consequently, multivalent molecules that express the same number of identical binding sites, but that differ in other structural features, can exhibit differences in their ability to discriminate between multivalent ligands. Here, Neil Greenspan and Laurence Cooper review evidence for these effects, and explore implications of the conclusion that effective specificity in multivalent interactions is not completely determined by the degree of complementarity between epitopes and paratopes.

[1]  F. A. Quiocho,et al.  Substrate specificity and affinity of a protein modulated by bound water molecules , 1989, Nature.

[2]  D E Leckband,et al.  Long-range attraction and molecular rearrangements in receptor-ligand interactions. , 1992, Science.

[3]  R. Zinkernagel,et al.  The influence of antigen organization on B cell responsiveness. , 1993, Science.

[4]  N. Greenspan,et al.  Fc region-dependence of IgG3 anti-streptococcal group A carbohydrate antibody functional affinity. I. The effect of temperature. , 1988, Journal of immunology.

[5]  K. Yamamoto,et al.  Crystallographic analysis of the interaction of the glucocorticoid receptor with DNA , 2003, Nature.

[6]  A. Lesk,et al.  Conformations of immunoglobulin hypervariable regions , 1989, Nature.

[7]  Robert Rosen,et al.  Fundamentals Of Measurement And Representation Of Natural Systems , 1978 .

[8]  N. Greenspan,et al.  Variable domain-identical antibodies exhibit IgG subclass-related differences in affinity and kinetic constants as determined by surface plasmon resonance. , 1994, Molecular immunology.

[9]  G. Lakoff,et al.  Women, Fire, and Dangerous Things: What Categories Reveal about the Mind , 1988 .

[10]  N. Greenspan,et al.  Role of heavy chain constant domains in antibody-antigen interaction. Apparent specificity differences among streptococcal IgG antibodies expressing identical variable domains. , 1993, Journal of immunology.

[11]  C. Milstein,et al.  Kinetic maturation of an immune response , 1991, Nature.

[12]  E. Mayr.  Toward a new philosophy of biology: observations of an evolutionist , 1988 .

[13]  C. Bindon,et al.  Complement activation by immunoglobulin does not depend solely on C1q binding , 1990, European journal of immunology.

[14]  D M Crothers,et al.  The influence of polyvalency on the binding properties of antibodies. , 1972, Immunochemistry.

[15]  I. Kuntz,et al.  Structure-based discovery of inhibitors of thymidylate synthase. , 1993, Science.

[16]  G. Lakoff.  Women, fire, and dangerous things : what categories reveal about the mind , 1989 .

[17]  E. Getzoff,et al.  Faster superoxide dismutase mutants designed by enhancing electrostatic guidance , 1992, Nature.

[18]  A. Schepartz,et al.  Altered specificity of DNA-binding proteins with transition metal dimerization domains. , 1993, Science.

[19]  I. Wilson,et al.  Structural evidence for induced fit as a mechanism for antibody-antigen recognition. , 1994, Science.

[20]  R. Rothlein,et al.  Isotype choice for chimeric antibodies affects binding properties. , 1994, The Journal of biological chemistry.

[21]  N. Greenspan,et al.  Intermolecular cooperativity: a clue to why mice have IgG3? , 1992, Immunology today.

[22]  S. Pincus,et al.  Studies on antigen binding by intact and hinge-deleted chimeric antibodies. , 1993, Journal of immunology.

[23]  N. Greenspan,et al.  Interaction of IgG3 anti-streptococcal group A carbohydrate (GAC) antibody with streptococcal group A vaccine: enhancing and inhibiting effects of anti-GAC, anti-isotypic, and anti-idiotypic antibodies. , 1987, Journal of immunology.

[24]  E. Mayr,et al.  Toward a New Philosophy of Biology , 1988 .

[25]  V. Parsegian,et al.  Protein solvation in allosteric regulation: a water effect on hemoglobin. , 1992, Science.

[26]  S. Del Río,et al.  The function of individual zinc fingers in sequence-specific DNA recognition by transcription factor IIIA. , 1993, Journal of molecular biology.

[27]  B. Kosko.  Fuzzy Thinking: The New Science of Fuzzy Logic , 1993 .

[28]  Steven M. Lipkin,et al.  The orientation and spacing of core DNA-binding motifs dictate selective transcriptional responses to three nuclear receptors , 1991, Cell.

[29]  Marvin Johnson,et al.  Concepts and applications of molecular similarity , 1990 .

[30]  E. Kabat.  Structural Concepts in Immunology and Immunochemistry , 1968 .

[31]  N. Greenspan,et al.  H chain C domains influence the strength of binding of IgG for streptococcal group A carbohydrate. , 1991, Journal of immunology.

[32]  N. Greenspan,et al.  Cooperative binding of two antibodies to independent antigens by an Fc‐dependent mechanism , 1989, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[33]  M Levitt,et al.  Water: now you see it, now you don't. , 1993, Structure.

[34]  L. Pauling,et al.  THE NATURE OF THE INTERMOLECULAR FORCES OPERATIVE IN BIOLOGICAL PROCESSES. , 1940, Science.