Immunogenicity

Abstract

An antigen refers to a molecule that is able to bind to the cells of the immune system. If an antigen can also stimulate an immune response, it is termed an immunogen. Immunogenicity is a measure of this ability to activate the immune response: that is, the B and T cells underlying humoral and cellā€mediated immunity. Understanding the concept of immunogenicity is therefore vital in understanding the field of immunology as a whole. The determinants of immunogenicity are complex, but much research has been conducted in this area in the context of vaccination and protein therapeutics, where understanding immunogenicity is of key clinical significance. While obtaining accurate measures of immunogenicity is difficult, a range of techniques to both predict the immunogenicity of a substance and to measure immunogenicity based on B and T cell activation have been developed.

Key Concepts

  • Immunogenicity is defined as the ability of a substance to elicit an adaptive immune response.
  • The immunogenicity of a substance depends on multiple factors relating to the properties of the substance itself, the biological system, and how the substance is delivered to the biological system.
  • Immunogenicity is necessary for our body to respond to and destroy pathogens, as well as to remove tumourogenic and dying cells.
  • Understanding immunogenicity is important for pharmaceutical development, where it is sometimes necessary to either increase (vaccination) or decrease (protein therapeutics) the immunogenicity of a product.
  • Experimental model systems, and more recently, computational tools, are being developed to predict immunogenicity.
  • Immunogenicity can be measured empirically by assessing the numbers of activated T or B cells, or antibody levels during a response to the substance.

Keywords: immunology; immunoregulation ; adaptive immunity; T cells; B cells; antigen; vaccination; protein therapeutics

Figure 1. The adaptive immune response. After an immunogenic substance enters a biological system, multiple pathways are activated to produce an adaptive immune response. The antigen is endocytosed by antigen‐presenting cells (including B cells), and presented on their surface in an antigen–MHC II complex. Cognate CD4 T cells interact with the antigen–MHC II complex to become activated. Further T cell activation occurs through interaction of the CD80/CD28 co‐stimulatory surface receptors. The first step of B cell activation occurs by direct binding of their B cell receptor (BCR) to the antigen. The second step of B cell activation then occurs either via activation of nonspecific surface receptors (TI‐1), extensive cross‐linking of the BCR (TI‐2), or by interaction with a CD4 T cell interacting with the antigen‐MHC complex on the B cell with the co‐receptors CD40/CD40L (TD). Once activated, the B cell proliferates, and differentiates into plasma cells, which produce antibody and memory cells to mediate long‐lasting protection. Interacting with the antigen–MHC I complex on infected cells activates CD8 T cells. Activated CD4 and CD8 T cells also differentiate to produce memory cells. Dotted red boxes indicate the initial effector cells of the adaptive immune response that can be measured to quantify immunogenicity.
Figure 2. Factors affecting immunogenicity. Immunogenicity of a substance is influenced by multiple properties of the antigenic substance, the biological host and features of delivery of the substance into the host. The figure details some of the main factors known to affect immunogenicity.
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Galson, Jacob D, and O'Connor, Daniel(Jul 2015) Immunogenicity. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000937]