Characteristics of Immunogenicity

CHARACTERISTICS OF IMMUNOGENICITY

Many different substances can induce immune responses. The following characteristics in-fluence the ability of a substance to behave as an immunogen:

Foreignness. As a rule, only substances recognized as nonself will trigger theimmune response. Microbial products and exogenous molecules are obviously nonself and may be strongly immunogenic.

Molecular Size. The most potent immunogens are macromolecular proteins[molecular weight (MW)>100,000 daltons]. Molecules smaller than 10,000 daltons are often only weakly immunogenic, unless coupled to an immunogenic carrier protein.

Chemical Structure. Proteins and polysaccharides are among the most potent im- munogens, although relatively small polypeptide chains, nucleic acids, and even lipids can, given the appropriate circumstances, be immunogenic. (a) Proteins: Large heterologous proteins express a wide diversity of antigenic determinants and are potent immunogens. It must be noted that the immunogenicity of a protein is strongly influenced by its chemical composition. Positively charged (basic) amino acids, such as lysine, arginine, and histidine, are repeatedly present in the antigenic sites of lysozyme and myoglobin, while aromatic amino acids (e.g., tyrosine) are found in two of six antigenic sites defined in albumin. Therefore, it appears that ba-sic and aromatic amino acids may contribute more strongly to immunogenicity thanother amino acids. Thus, basic proteins with clusters of positively charged amino acids are strongly immunogenic. (b) Polysaccharides: Polysaccharides are among the most important antigens because of their abundant representation in nature. Pure polysaccharides, the sugar moieties of glycoproteins, lipopolysaccharides, glycolipid-protein complexes, etc., are all immunogenic. Many microorganisms have polysaccharide-rich capsules or cell walls, and a variety of mammalian anti-gens, such as the erythrocyte antigens (A, B, Le, H), are short-chain polysaccha-rides (oligosaccharides). As noted later, polysaccharides and oligosaccharides stimulate B cells without promoting T-cell help. This is probablya result of the lack of binding of oligosaccharides to MHC-II molecules, resulting in the inability to activate helper T cells. (c) Nucleic acids: Nucleic acids (RNA and DNA) usually are not immunogenic, but they can induce antibody formation if coupled to a protein to form a nucleoprotein. The autoimmune responses charac-teristic of some of the so-called autoimmune diseases (e.g., systemic lupus erythe-matosus) are often directed to DNA and RNA. (d) Polypeptides: Hormones such as insulin and other polypeptides, although relatively small in size (MW 1500), are usually able to induce antibody formation when isolated from one species and ad-ministered over long periods of time to an individual of a different species.

Chemical complexity. There appears to be a direct relationship between anti-genicity and chemical complexity: aggregated or chemically polymerized pro-teins are much stronger immunogens than their soluble monomeric counterparts.