H. GIDEON WELLS 



703 



antibodies are sometimes referred to as "residue antigens" (Zinsser), and will be dis- 

 cussed in another chapter.' 



NATtHRE OF ANTIGENS 



Practically, antigens are proteins. There are few proteins that are not antigenic, 

 and it is not yet conclusively established that anything else can function as antigens. 

 In order that a protein may exhibit its antigenic effects it must be (i) soluble in the 

 fluids of the injected animal, in order that it may come in contact with the tissue 

 elements that react to form antibodies; (2) foreign to the active tissues of the animal, 

 for tissues are not stimulated to form antibodies by the proteins with which they are 

 normally in contact; (3) a complete or nearly complete protein molecule, possessed 

 of at least a certain minimum size and complexity. 



To explain more fully these essentials: 



1. Insoluble proteins, and proteins coagulated by heat or other means, which are 

 insoluble in the body fluids, are not antigenic, but proteins that have been coagulated 

 without losing their solubiUty (e.g., casein precipitated by weak acid, serum albumin 

 coagulated by alcohol) retain their antigenic activity. Therefore the changes induced 

 in the protein molecules during coagulation are not responsible for loss of antigenic 

 activity, but it is only the absence of solubility that renders proteins inactive. This is 

 corroborated by the fact that proteins that are not coagulated by brief boiling (e.g., 

 casein, mucoids) do not lose their antigenic capacity when boiled. 



2. As a general rule, the more closely related the animal furnishing the antibodies 

 is to the one furnishing the antigen the less antigenic activity or antibody response 

 will be obtained. Thus, it is difficult or impossible to secure antibodies by immunizing 

 a rabbit with the serum of a hare, or a dog with the blood of a fox. However, even in 

 unrelated species there may be some proteins that are similar, and hence exhibit low 

 antigenic activity (e.g., many tissue proteins). On the other hand, some proteins 

 having structural or physical rather than metabolic functions may be so foreign to 

 the blood stream and the active tissues of the body that they incite antibody forma- 

 tion when introduced into the bloodstream of even the same animal from which they 

 came (e.g., crystalline lens of the eye). Furthermore, chemical alterations in the 

 proteins of an animal may render them sufficiently foreign so that they can react as 

 antigens in that same animal. 



3. Certain amino-acid complexes, closely related to typical antigenic proteins, 

 lack antigenic capacity. Gelatin is the best-known example of this group. As gelatin 

 is not a natural protein, but one derived from collagen by hydrolysis, it is possible 

 that it is non-antigenic because it is not a complete protein. Chemically it is char- 

 acterized by its deficiency in aromatic radicals, for it contains no tryptophan, little 

 or no tyrosine, and not much phenyl alanine, but it is not known whether this de- 

 ficiency in aromatic radicals is responsible for the absence of antigenic capacity. We do 

 know that proteins may lack some of the usual amino acids of proteins and still be 

 antigenic, e.g., zein, which lacks tryptophan, lysine, and glycine; or casein, which lacks 

 cystine and glycine. On the other hand, such near-proteins as the protamines and 

 histones, which consist chiefly of diamino acids (histidine, lysine, arginine) with but 



' See chap, lii by Drs. Zinsser and Mueller in this volume. 



