Antigen

In immunology, an antigen (Ag), abbreviation of antibody generator, is any structural substance which serves as a target for the receptors of an adaptive immune response, TCR or BCR or its secreted form antibody, respectively. Each antibody is specifically selected after binding to a certain antigen because of random somatic diversification in the antibody complementarity determining regions (a common analogy used to describe this is the fit between a lock and a key). Paul Ehrlich coined the term antibody (in German Antikörper) in his side-chain theory at the end of 19th century. In summary, an antigen is a molecule that binds to Ag-specific receptors but cannot induce an immune response in the body by itself. Antigen was originally a structural molecule that binds specifically to the antibody, but the term now also refers to any molecule or a linear fragment that can be recognized by highly variable antigen receptors (B-cell receptor or T-cell receptor) of the adaptive immune system. The antigen may originate from within the body (“self”) or from the external environment (“non-self”). The immune system is usually non-reactive against “self” antigens under normal homeostatic conditions due to negative selection of T cells in the thymus and is supposed to identify and attack only “non-self” invaders from the outside world or modified/harmful substances present in the body under distressed conditions. Antigen presenting cells present the antigen structures in the form of processed antigenic peptides to the T cells of the adaptive immune system via a histocompatibility molecule. Depending on the antigen presented and the type of the histocompatibility molecule, several types of T cells can become activated. For T-Cell Receptor (TCR) recognition, it must be processed into small fragments inside the cell and presented to a T-cell receptor by major histocompatibility complex (MHC). Antigen by itself is not capable to elicit the immune response without the help of an Immunologic adjuvant. The essential role of the adjuvant component of vaccines in the activation of innate immune system is so-called immunologist’s dirty little secret as originally described by Charles Janeway. An immunogen is an analogy to the antigen a substance (or a mixture of substances) that is able to provoke an immune response if injected to the body. An immunogen is able to initiate an indispensable innate immune response first, later leading to the activation of the adaptive immune response, whereas an antigen is able to bind the highly variable immunoreceptor products (B-cell receptor or T-cell receptor) once these have been generated previously. Therefore, the overlapping concepts of immunogenicity and antigenicity are clearly different. According to current textbook notions: Immunogenicity is the ability to induce a humoral and/or cell-mediated immune response Antigenicity is the ability to combine specifically with the final products of the immune response (i.e. secreted antibodies and/or surface receptors on T-cells). Although all immunogenic molecules are also antigenic, the reverse is not true. At the molecular level, an antigen can be characterized by its ability to be bound by the variable Fab region of an antibody. Note also that different antibodies have the potential to discriminate between specific epitopes present on the surface of the antigen (as illustrated in the Figure). Hapten is a small molecule that changes the structure of an antigenic epitope. In order to induce an immune response, it has to be attached to a large carrier molecule such as protein. Antigens are usually proteins and polysaccharides, less frequently also lipids. This includes parts (coats, capsules, cell walls, flagella, fimbrae, and toxins) of bacteria, viruses, and other microorganisms. Lipids and nucleic acids are antigenic only when combined with proteins and polysaccharides. Non-microbial exogenous (non-self) antigens can include pollen, egg white, and proteins from transplanted tissues and organs or on the surface of transfused blood cells. Vaccines are examples of antigens in an immunogenic form, which are to be intentionally administered to induce the memory function of adaptive immune system toward the antigens of the pathogen invading the recipient.