Antigen
In
Antigens can be
Antigens are recognized by antigen receptors, including antibodies and T-cell receptors.
Antigen can originate either from within the body ("self-protein" or "self antigens") or from the external environment ("non-self").[2] 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.[5] The diseases in which antibodies react with self antigens and damage the body's own cells are called autoimmune diseases.[6]
Etymology
Paul Ehrlich coined the term antibody (German: Antikörper) in his side-chain theory at the end of the 19th century.[8] In 1899, Ladislas Deutsch (László Detre) named the hypothetical substances halfway between bacterial constituents and antibodies "antigenic or immunogenic substances" (French: substances immunogènes ou antigènes). 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 (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".[9] The term originally referred to a substance that acts as an antibody generator.[10]
Terminology
- idiotypes, each have distinctly formed complementarity-determining regions.
- 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.
- molecular form. If its molecular form is changed, a tolerogen can become an immunogen.
- that are capable of binding to antibodies at positions outside of the antigen-binding site. While antigens are the "target" of antibodies, immunoglobulin-binding proteins "attack" antibodies.
- T-dependent antigen – Antigens that require the assistance of T cells to induce the formation of specific antibodies.
- T-independent antigen – Antigens that stimulate B cells directly.
- Immunodominant antigens – Antigens that dominate (over all others from a pathogen) in their ability to produce an immune response. T cell responses typically are directed against a relatively few immunodominant epitopes, although in some cases (e.g., infection with the malaria pathogen Plasmodium spp.) it is dispersed over a relatively large number of parasite antigens.[11]
An immunogen is an antigen substance (or
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. A hapten is a small molecule that can only induce an immune response when attached to a larger carrier molecule, such as a protein. Antigens can be proteins, polysaccharides, lipids, nucleic acids or other biomolecules.[4] This includes parts (coats, capsules, cell walls, flagella, fimbriae, and toxins) 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.
Sources
Antigens can be classified according to their source.
Exogenous antigens
Exogenous antigens are antigens that have entered the body from the outside, for example, by
Some antigens start out as exogenous and later become endogenous (for example, intracellular viruses). Intracellular antigens can be returned to circulation upon the destruction of the infected cell.
Endogenous antigens
Endogenous antigens are generated within normal cells as a result of normal cell
Autoantigens
An autoantigen is usually a self-protein or protein complex (and sometimes DNA or RNA) that is recognized by the immune system of patients with a specific autoimmune disease. Under normal conditions, these self-proteins should not be the target of the immune system, but in autoimmune diseases, their associated T cells are not deleted and instead attack.
Neoantigens
Neoantigens are those that are entirely absent from the normal human genome. As compared with nonmutated self-proteins, neoantigens are of relevance to tumor control, as the quality of the T cell pool that is available for these antigens is not affected by central T cell tolerance. Technology to systematically analyze T cell reactivity against neoantigens became available only recently.[18] Neoantigens can be directly detected and quantified.[19]
Viral antigens
For virus-associated tumors, such as
Tumor antigens
Tumor antigens can appear on the surface of the tumor in the form of, for example, a mutated receptor, in which case they are recognized by
For human tumors without a viral etiology, novel
Process
A large fraction of human tumor mutations are effectively patient-specific. Therefore, neoantigens may also be based on individual tumor genomes. Deep-sequencing technologies can identify mutations within the protein-coding part of the
The false-negative rate of cancer exome sequencing is low—i.e.: the majority of neoantigens occur within exonic sequence with sufficient coverage. However, the vast majority of mutations within expressed genes do not produce neoantigens that are recognized by autologous T cells.[18]
As of 2015 mass spectrometry resolution is insufficient to exclude many false positives from the pool of peptides that may be presented by MHC molecules. Instead, algorithms are used to identify the most likely candidates. These algorithms consider factors such as the likelihood of proteasomal processing, transport into the endoplasmic reticulum, affinity for the relevant MHC class I alleles and gene expression or protein translation levels.[18]
The majority of human neoantigens identified in unbiased screens display a high predicted MHC binding affinity. Minor histocompatibility antigens, a conceptually similar antigen class are also correctly identified by MHC binding algorithms. Another potential filter examines whether the mutation is expected to improve MHC binding. The nature of the central TCR-exposed residues of MHC-bound peptides is associated with peptide immunogenicity.[18]
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
Antigenic 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 measurable and need not be linear or of a rate-limited step or equation.[2][7] Both T cells and B cells are cellular components of adaptive immunity.[2][4]
See also
References
- ^ a b "Antibody". National Human Genome Research Institute, US National Institutes of Health. 2020. Retrieved 13 October 2020.
- ^ a b c d e "Immune system and disorders". MedlinePlus, US National Institute of Medicine. 28 September 2020. Retrieved 13 October 2020.
- ^ a b c d "Antigen". Cleveland Clinic. 2023. Retrieved 23 May 2023.
- ^ OCLC 1002110073.
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- ^ a b "Antigenic characterization". US Centers for Disease Control and Prevention. 15 October 2019. Retrieved 13 October 2020.
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- ^ Parham, Peter. (2009). The Immune System, 3rd Edition, p. G:2, Garland Science, Taylor and Francis Group, LLC.
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- ^ Parham, Peter. (2009). The Immune System, 3rd Edition, p. G:11, Garland Science, Taylor and Francis Group, LLC.
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