In immunology, an antigen is a substance that evokes the production of one or more antibodies. Each antibody binds to a specific antigen by way of an interaction similar to the fit between a lock and a key. The substance may be from the external environment or formed within the body. The immune system will try to destroy or neutralize any antigen that is recognized as a foreign and potentially harmful invader. The term originally came from antibody generator^[1][2] and was a molecule that binds specifically to an antibody, but the term now also refers to any molecule or molecular fragment that can be bound by a major histocompatibility complex (MHC) and presented to a T-cell receptor.^[3] "Self" antigens are usually tolerated by the immune system; whereas "Non-self" antigens can be identified as invaders and can be attacked by the immune system.

An immunogen is a specific type of antigen. An immunogen is a substance that is able to provoke an adaptive immune response if injected on its own.^[4] An immunogen is able to induce an immune response, whereas an antigen is able to combine with the products of an immune response once they are made. The overlapping concepts of immunogenicity and antigenicity are, therefore, subtly different. According to a current textbook:

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 molecules that have the property of immunogenicity also have the property of antigenicity, the reverse is not true."^[5]

At the molecular level, an antigen is characterized by its ability to be "bound" at the antigen-binding site of an antibody. Note also that antibodies tend to discriminate between the specific molecular structures presented on the surface of the antigen (as illustrated in the Figure). Antigens are usually proteins or polysaccharides. 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 immunogenic antigens intentionally administered to induce acquired immunity in the recipient.

Cells present their immunogenic-antigens to the immune system via a histocompatibility molecule. Depending on the antigen presented and the type of the histocompatibility molecule, several types of immune cells can become activated.

Related concepts[link]

• Epitope - The distinct molecular surface features of an antigen capable of being bound by an antibody (a.k.a. antigenic determinant). Antigenic molecules, normally being "large" biological polymers, usually present several surface features that can act as points of interaction for specific antibodies. Any such distinct molecular feature constitutes an epitope. Therefore, most antigens have the potential to be bound by several distinct antibodies, each of which is specific to a particular epitope. Using the "lock and key" metaphor, the antigen itself can be seen as a string of keys - any epitope being a "key" - each of which can match a different lock. Different antibody idiotypes, each having distinctly formed complementarity determining regions, correspond to the various "locks" that can match "the keys" (epitopes) presented on the antigen molecule.

• Allergen - A substance capable of causing an allergic reaction. The (detrimental) reaction may result after exposure via ingestion, inhalation, injection, or contact with skin.
• Superantigen - A class of antigens that cause non-specific activation of T-cells, resulting in polyclonal T cell activation and massive cytokine release.
• Tolerogen - A substance that invokes a specific immune non-responsiveness due to its molecular form. If its molecular form is changed, a tolerogen can become an immunogen.
• Immunoglobulin binding protein - These proteins are capable of binding to antibodies at positions outside of the antigen-binding site. That is, whereas antigens are the "target" of antibodies, immunoglobulin-binding proteins "attack" antibodies. Protein A, protein G, and protein L are examples of proteins that strongly bind to various antibody isotypes.

Origin of the term antigen[link]

In 1899, Ladislas Deutsch (Laszlo Detre) (1874–1939) named the hypothetical substances halfway between bacterial constituents and antibodies "substances immunogenes ou antigenes". He originally believed those substances to be precursors of antibodies, just like zymogen is a precursor of an enzyme. But, by 1903, he understood that an antigen induces the production of immune bodies (antibodies) and wrote that the word antigen is a contraction of "Antisomatogen = Immunkörperbildner". The Oxford English Dictionary indicates that the logical construction should be "anti(body)-gen".^[6]

Origin of antigens[link]

Antigens can be classified in order of their class.

Exogenous antigens[link]

Exogenous antigens are antigens that have entered the body from the outside, for example by inhalation, ingestion, or injection. The immune system's response to exogenous antigens is often subclinical. By endocytosis or phagocytosis, exogenous antigens are taken into the antigen-presenting cells (APCs) and processed into fragments. APCs then present the fragments to T helper cells (CD4⁺) by the use of class II histocompatibility molecules on their surface. Some T cells are specific for the peptide:MHC complex. They become activated and start to secrete cytokines. Cytokines are substances that can activate cytotoxic T lymphocytes (CTL), antibody-secreting B cells, macrophages, and other particles.

Some antigens start out as exogenous antigens, and later become endogenous (for example, intracellular viruses). Intracellular antigens can be released back into circulation upon the destruction of the infected cell, again.

Endogenous antigens[link]

Endogenous antigens are antigens that have been generated within previously-normal cells as a result of normal cell metabolism, or because of viral or intracellular bacterial infection. The fragments are then presented on the cell surface in the complex with MHC class I molecules. If activated cytotoxic CD8⁺ T cells recognize them, the T cells begin to secrete various toxins that cause the lysis or apoptosis of the infected cell. In order to keep the cytotoxic cells from killing cells just for presenting self-proteins, self-reactive T cells are deleted from the repertoire as a result of tolerance (also known as negative selection). Endogenous antigens include xenogenic (heterologous), autologous and idiotypic or allogenic (homologous) antigens.

Autoantigens[link]

An autoantigen is usually a normal protein or complex of proteins (and sometimes DNA or RNA) that is recognized by the immune system of patients suffering from a specific autoimmune disease. These antigens should, under normal conditions, not be the target of the immune system, but, due to mainly genetic and environmental factors, the normal immunological tolerance for such an antigen has been lost in these patients.

Tumor antigens[link]

Tumor antigens or neoantigens are^{[citation needed]} those antigens that are presented by MHC I or MHC II molecules on the surface of tumor cells. These antigens can sometimes be presented by tumor cells and never by the normal ones. In this case, they are called tumor-specific antigens (TSAs) and, in general, result from a tumor-specific mutation. More common are antigens that are presented by tumor cells and normal cells, and they are called tumor-associated antigens (TAAs). Cytotoxic T lymphocytes that recognize these antigens may be able to destroy the tumor cells before they proliferate or metastasize.

Tumor antigens can also be on the surface of the tumor in the form of, for example, a mutated receptor, in which case they will be recognized by B cells.

Nativity[link]

A native antigen is an antigen that is not yet processed by an APC to smaller parts. T cells cannot bind native antigens, but require that they be processed by APCs, whereas B cells can be activated by native ones.

Antigenic specificity[link]

Antigen(ic) specificity is the ability of the host cells to recognize an antigen specifically as a unique molecular entity and distinguish it from another with exquisite precision. Antigen specificity is due primarily to the side-chain conformations of the antigen. It is a measurement, although the degree of specificity may not be easy to measure, and need not be linear or of the nature of a rate-limited step or equation.^[7]

See also[link]

• Epitope
• Linear epitope
• Conformational epitope
• Original antigenic sin
• Polyclonal B cell response
• Magnetic immunoassay
• Priming (immunology)

Notes[link]

External links[link]

• Antigen Retrieval Protocol
• Immunology
• National Library of Medicine/Medline (National Institute of Health) website

Ira Mellman, Ph.D. is an American cell biologist who discovered endosomes^[1]. He serves as Vice President of Research Oncology at Genentech in South San Francisco, California and is Professor of Biochemistry & Biophysics at the University of California, San Francisco.^[2]

Research[link]

Mellman's work has examined the role of endocytosis in cell metabolism and human disease. He was among the first to characterize the endosomal system. Later projects include investigation of LDL cholesterol receptor internalization, cellular sorting machinery, and the cellular basis for immunity. He is an authority on the cell biological mechanisms and function of dendritic cells, the cell type responsible for initiating the immune response, an interest that dates back to his postdoctoral period at Rockefeller University in the lab of Ralph Steinman, who won the Nobel Prize in 2011 for his discovery of dendritic cells.

Early Life and Studies[link]

Mellman grew up in New York, where he lived until he enrolled at Oberlin College in Oberlin, Ohio. While in college he maintained an interest in music but focused on the rapidly expanding field of cell biology.

Move to Yale and Later Years[link]

After leaving Oberlin, he enrolled in the graduate program at the University of California, Berkeley, but later transferred to Yale University. He returned to Yale after completing postdoctoral work and remained there as a professor for over twenty years. During this time he was the Sterling Professor of Cell Biology & Immunobiology, chair of the Cell Biology Department, Scientific Director of the Yale Cancer Center and a member of the Ludwig Institute for Cancer Research. Mellman has served on the council of the American Society for Cell Biology and was the editor-in-chief of the Journal of Cell Biology from 1999-2008, he remains active as a Senior Editor for the journal.

Mellman is a member of the US National Academy of Sciences^[2], a Fellow of the American Academy of Arts and Sciences, and a Foreign Associate of the European Molecular Biology Organization (EMBO).

In 1977, he married Margaret Moench; the couple have three children.

Trivia[link]

• Mellman keeps a picture of former WTOP reporter and anchorman Ira Mellman on the front of his door.
• Mellman plays bass in his own rock band called "The Cellmates."

References[link]

External links[link]

• The American Society for Cell Biology
• Yale Cancer Center Newsletter

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