Antigen


In immunology, an antigen is a molecule, or portion thereof, that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response.
Antigens can be proteins, peptides, polysaccharides, lipids, or nucleic acids. Antigens exist on normal cells, cancer cells, parasites, viruses, fungi, and bacteria.
Antigens are recognized by antigen receptors, including antibodies and T-cell receptors. Diverse antigen receptors are made by cells of the immune system so that each cell has a specificity for a single antigen. Upon exposure to an antigen, only the lymphocytes that recognize that antigen are activated and expanded, a process known as clonal selection. In most cases, antibodies are antigen-specific, meaning that an antibody can only react to and bind one specific antigen; in some instances, however, antibodies may cross-react to bind more than one antigen. The reaction between an antigen and an antibody is called the antigen-antibody reaction.
Antigen can originate either from within the body or from the external environment. The immune system identifies and attacks "non-self" external antigens. Antibodies usually do not react with self-antigens due to negative selection of T cells in the thymus and B cells in the bone marrow. The diseases in which antibodies react with self antigens and damage the body's own cells are called autoimmune diseases.
Vaccines are examples of antigens in an immunogenic form, which are intentionally administered to a recipient to induce the memory function of the adaptive immune system towards antigens of the pathogen invading that recipient. The vaccine for seasonal influenza is a common example.

Etymology

coined the term antibody in his side-chain theory at the end of the 19th century. In 1899, Ladislas Deutsch named the hypothetical substances halfway between bacterial constituents and antibodies "antigenic or immunogenic substances". He originally believed those substances to be precursors of antibodies, just as a zymogen is a precursor of an enzyme. But, by 1903, he understood that an antigen induces the production of immune bodies and wrote that the word antigen is a contraction of antisomatogen. The Oxford English Dictionary indicates that the logical construction should be "anti-gen".
The term originally referred to a substance that acts as an antibody generator.

Terminology

Antigens can be proteins, polysaccharides, lipids, nucleic acids or other biomolecules. This includes parts of bacteria, viruses, and other microorganisms. Non-microbial non-self antigens can include pollen, egg white, and proteins from transplanted tissues and organs or on the surface of transfused blood cells.
  • Immunogen — an antigen that is capable of inducing an immune response, i.e., it is immunogenic. Antigen is often used interchangeably with this term, but this is not, strictly speaking, correct. All immunogens are antigens, but not all antigens are immunogens. The antigen within a vaccine is often referred to as an immunogen, even if, strictly speaking, its purified form cannot induce immune responses. For simplicity, many sources use the term "antigen" in place of "immunogen," but these terms should not be regarded as interchangeable.
  • Allergen – A substance capable of causing an allergic reaction in sensitized individuals. The reaction may result after exposure via ingestion, inhalation, injection, or contact with skin.
  • Tolerogen – A substance that invokes immune tolerance. This property is related to its molecular properties and circumstances such as route of administration.
  • Superantigen – A class of antigens that cause non-specific activation of T-cells, resulting in polyclonal T-cell activation and massive cytokine release.
  • Immunoglobulin-binding protein – Proteins such as protein A, protein G, and protein L that are capable of binding to antibodies at positions outside of the antigen-binding site. These are sometimes known as B cell superantigens.
  • Epitope – The specific part of an antigen that is bound by an antibody, its antigenic determinant.
Antigenic molecules, normally "large" biological polymers, usually present surface features that can act as points of interaction for specific antibodies. Any such feature constitutes an epitope. Most antigens have the potential to be bound by multiple antibodies, each of which is specific to one of the antigen's epitopes. Using the "lock and key" metaphor, the antigen can be seen as a string of keys each of which matches a different lock. Different antibody idiotypes, each have distinctly formed complementarity-determining regions. Antibodies may compete for binding when they recognize overlapping epitopes.
  • Paratope — The specific part of the antibody that binds the antigen.
  • Agretope — The specific peptide sequence recognized by a major histocompatibility complex.
  • Hapten — A small molecule that can only induce an immune response when attached to a larger carrier molecule, such as a protein. The hapten alone will not be recognized if not associated with a carrier.
  • T-dependent antigen – Antigens that require the assistance of T cells to induce the formation of specific antibodies.
  • T-independent antigen – Antigens that can induce the production of antibodies without the help of T cells.
  • * T-independent type I antigen — Mitogens that induce nonspecific activation of B cells
  • * T-independent type II antigen — Antigens containing multiple repetitive motifs that allow them to crosslink B cell receptors and directly activate the B cells. Bacterial capsule polysaccharides are a common example.
  • Immunodominant antigens – Antigens that dominate in their ability to produce an immune response. T cell responses typically are directed against a relatively few immunodominant epitopes, although in some cases it is dispersed over a relatively large number of parasite antigens. These are contrasted with immunosubdominant antigens.
Antigen-presenting cells present antigens in the form of peptides on major histocompatibility complexes. All nucleated cells express MHC class I, which samples peptides from the cytosol, defaulting to presenting self-antigen. Antigens originating from outside the cell make their way into the endomembrane system via processes like phagocytosis, endocytosis, or macropinocytosis and are loaded onto MHC class II molecules. In contrast to MHC class I, MHC class II is expressed on a limited subset of cells, the vast majority of which are immune cells. Often, when people refer to antigen-presenting cells, they are actually referring to professional antigen-presenting cells. Professional antigen-presenting cells refer to B cells, dendritic cells, Langerhans cells, and macrophages, all of which express MHC class II and have the ability to activate naive T cells. The MHC locus is the most polymorphic region of the entire human genome, and it is responsible for the presentation of antigens to T cells. This extensive polymorphism provides population-level protection by increasing the likelihood that some individuals will mount effective immune responses against novel pathogens, thus helping to ensure species survival during epidemics. Cheetahs, for example, underwent a bottleneck event 10,000 years ago that greatly limited the diversity of their MHC locus and as a result, show increased susceptibility to infectious diseases, though this represents one of multiple factors affecting their conservation status.
CD4 T cells are able to recognize MHC class II molecules using CD4, and their T-cell receptor recognizes the specific peptide-MHC complex sequence. In contrast, CD8 T cells are able to recognize MHC class I molecules through the α3 domain of MHC class I. T cell receptors are, in general, highly specific to particular peptide-MHC complexes. Some peptide sequences can only be presented by a specific type of MHC protein because they require specific amino acid sequences within the binding groove to associate with them. These are known as MHC-restricted peptides. If an individual does not express the relevant MHC protein needed for a given MHC-restricted peptide, they will not be able to present that antigen to T cells. This can be an important consideration in the design of vaccines, as a robust immune response should be generated in every vaccinee, which will not be possible if it has too many MHC-restricted peptide sequences and the vaccinee does not express the correct MHC polymorphism for effective presentation to T cells. Because the T cell receptor cannot recognize anything not presented on an MHC, conventional T cells are not capable of responding to non-peptide antigens, except in the case of post-translational modifications to peptides that end up being presented. This is important because polysaccharide vaccines elicit antibody responses without T cell help, and as a result, those antibody responses tend to be weak and short-lived. However, attaching the polysaccharide to a carrier protein enables B cells that recognize the polysaccharide to get help from T cells that recognize the carrier protein's peptides. These are known as conjugate vaccines or glycoconjugates. Moreover, the processing of an antigen by an antigen-presenting cell causes loss of the tertiary structure of the protein, meaning that T cells recognize linear epitopes only.
There are also subsets of T cells known as unconventional T cells that may recognize non-peptide antigens, or peptides. Many of these subsets show predominantly innate, rather than adaptive, functions. For example, γδ T cells express a T-cell receptor comprising γ and δ chains instead of the α and β chains that conventional T cell receptors use, and they are able to recognize antigen without the need for presenting it on MHC proteins, instead having a mode of recognition that resembles that of antibodies, or recognizing phosphoantigens through butyrophilin. Mucosa-associated invariant T cells cells recognize ligands presented by the MHC-related protein MR1, which presents metabolites of riboflavin, pyridoxine, and folates. NKT cells recognize glycolipid antigens presented on CD1d, most prominently α-galactosylceramide.
In contrast to T cell receptors, antibodies can recognize any type of molecule at virtually any size and can recognize either linear or conformational epitopes. At the molecular level, an antigen can be characterized by its ability to bind to an antibody's paratopes. Different antibodies have the potential to discriminate among specific epitopes present on the antigen surface.