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The Journal of Immunology, 1941, 42: 515-530.
Copyright © 1941 by The American Association of Immunologists, Inc.

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A Descriptive Theory of Specific Precipitation

III. The Individuality of Antibody

A. D. Hershey

Department of Bacteriology and Immunology, Washington University School of Medicine, St. Louis, Mo.

Abstract

1. In the preceding paper, general expressions are derived foran hypothetical initial equilibrium between multivalent antigenand multivalent antibody, which form the basis for a
2. General theory of precipitation, which postulates a minimaldisturbance of the initial equilibrium during aggregation, and a
3. Restricted theory, which specifies the direction of disturbancesof the initial equilibrium if antigen and antibody areindeed multivalent.
4. For the special case of lattice-formation, the restrictedtheory is developed in a preliminary way to permit quantitativedescription of the composition of precipitates, and more fully todeal with flocculation-times and the meaning of optimal proportions.
5. The restricted theory leads to the concept of selective precipitation,which is probably adequate to explain the small volumeeffect observed in precipitating systems, and the different effectsof excess of either reagent.
6. The relation of structure .to the properties of lattices areconsidered in connection with the solubility of precipitates andthe problem of reversibility of biologic effects of antigen-antibodyreactions.
7. Experimental methods are suggested for the measurementof the parameters of lattice-systems, which are three: the maximalvalence of antigen, the maximal valence of antibody, and thedissociation-constant of the unit-valence. These, together withconcentration-factors, completely define an ideal lattice-system.
8. In the application of the theory to experimental precipitatingsystems additional parameters such as the homogeneity andfunctional symmetry of the reactants, and nonspecific associativeforces, are considered. In no case do available data clearly showthat these influences seriously prejudice the usefulness of thetheory. It is likely, however, that such instances will be found.
9. It is suggested that the principal parameter defining theindividuality of different immune sera to a given antigen is thedissociation-constant of the specific valence. At present thereis no reason to suppose that the diverse properties of differentantisera, including their specificity, in any way imply a correspondingdiversity of the fundamental immune response.
10. The unit-valence appears to represent an area of contactof the order 10—3 cm2. The relation between the dissociationconstantof the unit-valence and the structure of the antigenicsurface is discussed briefly. The dissociation-constant of theimmunologic valence is believed to be strongly influenced byassociated substances foreign to the specific antibody.
11. The evidence is overwhelmingly in favor of the hypothesisthat antibody and antigen are multivalent, and that the maximalvalence of antibody is small, probably two. The maximal valenceof antigen is probably limited primarily by the physical surfaceof the molecule.
12. Several definitions of practical usefulness are proposed inpart IIc.

The encouragement and instruction continuously offered byDr. Bronfenbrenner have contributed decisively to the resultsachieved in this study.







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