In immunology, an antigen, or antibody generator, is any substance which provokes an adaptive
immune response.
An antigen is often foreign or toxic to the body which, once in the body, attracts and
is bound to a respective and specific antibody.
That is to say, an antigen is a molecule that also induces an immune response in the body.
Each antibody is specifically designed to deal with certain antigens because of variation
in the antibody's complementarity determining regions.
Paul Ehrlich coined the term antibody in his side-chain theory at the end of 19th century.
The term antigen originally came from ANTIbody GENerator.
The antigen may originate from within the body or from the external environment.
The immune system is usually non-reactive against "self" antigens under normal conditions
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.
Cells present their antigenic structures 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.
Antigen was originally a structural molecule that binds specifically to the antibody, but
the term now also refers to any molecule or molecular fragment that can be recognized
by highly variable antigen receptors of the adaptive immune system.
For T-Cell Receptor recognition, it must be processed into small fragments inside the
cell and presented to a T-cell receptor by major histocompatibility complex.
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 in analogy to the antigen a substance 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 once these have been produced.
The overlapping concepts of immunogenicity and antigenicity are, therefore, subtly 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.
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.
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 of bacteria, viruses, and other microorganisms.
Lipids and nucleic acids are antigenic only when combined with proteins and polysaccharides.
Non-microbial exogenous 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.
Related concepts Epitope – The distinct molecular surface
features of an antigen capable of being bound by an antibody.
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 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 matching a different lock.
Different antibody idiotypes, each having distinctly formed complementarity determining
regions, correspond to the various "locks" that can match "the keys" presented on the
antigen molecule.
Allergen – A substance capable of causing an allergic reaction.
The 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.
T-dependent antigen – T-dependent antigens are usually proteins.
They require an assistance of T cells to induce the formation of specific antibodies.
T-independent antigen – T-independent antigens are usually polysaccharides stimulating B
cells directly.
Immunodominant antigens are the ones that dominate in their ability to produce an immune
response.
It is commonly assumed that T cell responses are directed against a relatively few immunodominant
epitopes, although at least in some cases it is dispersed over a relatively large number
of parasite antigens.
Origin of the term antigen In 1899, Ladislas Deutsch 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 as 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(= "Immunkörperbildner").
The Oxford English Dictionary indicates that the logical construction should be "anti(body)-gen".
Origin of antigens Antigens can be classified in order of their
class.
Exogenous antigens 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 and processed into fragments.
APCs then present the fragments to T helper cells 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, antibody-secreting
B cells, macrophages, and other particles.
Some antigens start out as exogenontigens, and later become endogenous.
Intracellular antigens can again be released back into circulation upon the destruction
of the infected cell.
Endogenous antigens 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.
Endogenous antigens include xenogenic, autologous and idiotypic or allogenic antigens.
Autoantigens An autoantigen is usually a normal protein
or complex of proteins that is recognized by the immune system of patients suffering
from a specific autoimmune disease.
These antigens should not be, under normal conditions, the target of the immune system,
but, due mainly to genetic and environmental factors, the normal immunological tolerance
for such an antigen has been lost in these patients.
Tumor antigens Tumor antigens or neoantigens are 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 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.
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 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 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.
See also Antitoxin
Conformational epitope Epitope
Linear epitope Magnetic immunoassay
Neutralizing antibody Original antigenic sin
Paul Ehrlich: Magic Bullet Polyclonal B cell response
Priming Notes
External links Antigen Retrieval Protocol
Immunology National Library of Medicine/Medline website