Factors That Influence Immunogenicity

Lecture 1.6 Antigens

Substances that can be recognized by the immunoglobulin receptor of B cells, or by the T cell receptor when complexed with MHC, are called antigens. The molecular properties of antigens and the way in which these properties ultimately contribute to immune activation are central to our understanding of the immune system. This lecture describes some of the molecular features of antigens recognized by B or T cells. The lecture also explores the contribution made to immunogenicity by the biological system of the host; ultimately the biological system determines whether a molecule that combines with a B or T cell’s antigen-binding receptor can then induce an immune response. Fundamental differences in the way B and T lymphocytes recognize antigen determine which molecular features of an antigen are recognized by each branch of the immune system.

Immunogenicity Versus Antigenicity

Immunogenicity and antigenicity are related but distinct immunologic properties that sometimes are confused. Immunogenicity is the ability to induce a humoral and/or cellmediated immune response:

Although a substance that induces a specific immune response is usually called an antigen, it is more appropriately called an immunogen.

Antigenicityis the ability to combine specifically with the final products of the above responses (i.e., antibodies and/or cell-surface receptors). Although all molecules that have the property of immunogenicity also have the property of antigenicity, the reverse is not true. Some small molecules, called haptens, are antigenic but incapable, by themselves, of inducing a specific immune response. In other words, they lack immunogenicity.

Factors That Influence Immunogenicity

To protect against infectious disease, the immune system must be able to recognize bacteria, bacterial products, fungi, parasites, and viruses as immunogens. In fact, the immune system actually recognizes particular macromolecules of an infectious agent, generally either proteins or polysaccharides. Proteins are the most potent immunogens, with polysaccharides ranking second. In contrast, lipids and nucleic acids of an infectious agent generally do not serve as immunogens unless they are complexed with proteins or polysaccharides. Immunologists tend to use proteins or polysaccharides as immunogens in most experimental studies of humoral immunity. For cell-mediated immunity, only proteins and some lipids and glycolipids serve as immunogens. These molecules are not recognized directly. Proteins must first be processed into small peptides and then presented together with MHC molecules on the membrane of a cell before they can be recognized as immunogens. Recent work shows that those lipids and glycolipids that can elicit cellmediated immunity must also be combined with MHC-like membrane molecules called CD1.

Immunogenicity is not an intrinsic property of an antigen but rather depends on a number of properties of the particular biological system that the antigen encounters. The next two sections describe the properties that most immunogens share and the contribution that the biological system makes to the expression of immunogenicity.