Editing Antigen (section)

==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 [[inhalation]], [[ingestion]] or [[Injection (medicine)|injection]]. The immune system's response to exogenous antigens is often subclinical. By [[endocytosis]] or [[phagocytosis]], exogenous antigens are taken into the [[antigen-presenting cell]]s (APCs) and processed into fragments. APCs then present the fragments to [[T helper cells]] ([[CD4]]<sup>+</sup>) by the use of [[MHC class II|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, substances that activate [[cytotoxic T lymphocytes]] (CTL), antibody-secreting [[B cell]]s, [[macrophages]] and other particles.

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 [[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 T cell|cytotoxic CD8<sup>+</sup> T cells]] recognize them, the T cells secrete various [[toxin]]s that cause the [[lysis]] or [[apoptosis]] of the infected cell. In order to keep the cytotoxic cells from killing cells just for presenting [[self-protein]]s, the cytotoxic cells (self-reactive T cells) are deleted as a result of [[Central tolerance|tolerance]] (negative selection). Endogenous antigens include [[xenogenic]] (heterologous), [[autologous]] and [[idiotype|idiotypic]] or [[immunoglobulin allotype|allogenic]] (homologous) antigens. Sometimes antigens are [[Autoimmunity|part of the host itself]] in an [[autoimmune disease]].<ref name=mlp/>

===Autoantigens===
An [[Self-protein|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.<ref name="ss15">{{cite journal | vauthors = Schumacher TN, Schreiber RD | title = Neoantigens in cancer immunotherapy | journal = Science | volume = 348 | issue = 6230 | pages = 69–74 | date = April 2015 | pmid = 25838375 | doi = 10.1126/science.aaa4971 | doi-access = free | bibcode = 2015Sci...348...69S }}</ref> Neoantigens can be directly detected and quantified.<ref name="ss16">{{cite journal | vauthors = Wang Q, Douglass J, Hwang MS, Hsiue EH, Mog BJ, Zhang M, Papadopoulos N, Kinzler KW, Zhou S, Vogelstein B | display-authors = 3 | title = Direct Detection and Quantification of Neoantigens | journal = Cancer Immunology Research | volume = 7 | issue = 11 | pages = 1748–1754 | date = November 2019 | pmid = 31527070 | pmc = 6825591 | doi = 10.1158/2326-6066.CIR-19-0107 }}</ref>

==== Viral antigens ====
For virus-associated tumors, such as [[cervical cancer]] and a subset of [[head and neck cancers]], [[epitope]]s derived from viral open reading frames contribute to the pool of neoantigens.<ref name=ss15/>

====Tumor antigens====<!-- This section is linked from [[Immune system]] -->
''[[Tumor antigen]]s'' are those antigens that are presented by [[MHC class I]] or [[MHC class II]] molecules on the surface of [[tumor cell]]s. Antigens found only on such cells are called [[tumor-specific antigen]]s (TSAs) and generally result from a tumor-specific [[mutation]]. More common are antigens that are presented by tumor cells and normal cells, called [[tumor-associated antigen]]s (TAAs). [[Cytotoxic T lymphocytes]] that recognize these antigens may be able to destroy tumor cells.<ref name=ss15/>

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 [[B cells]].<ref name=ss15/>

For human tumors without a viral etiology, novel [[peptides]] (neo-epitopes) are created by tumor-specific DNA alterations.<ref name=ss15/>

===== 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 [[genome]] (the [[exome]]) and predict potential neoantigens. In mice models, for all novel protein sequences, potential MHC-binding peptides were predicted. The resulting set of potential neoantigens was used to assess T cell reactivity. Exome–based analyses were exploited in a clinical setting, to assess reactivity in patients treated by either [[tumor-infiltrating lymphocyte]] (TIL) cell therapy or checkpoint blockade. Neoantigen identification was successful for multiple experimental model systems and human malignancies.<ref name="ss15" />

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.<ref name="ss15" />

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 [[proteasome|proteasomal]] processing, transport into the [[endoplasmic reticulum]], affinity for the relevant MHC class I [[allele]]s and gene expression or protein translation levels.<ref name="ss15" />

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.<ref name="ss15" />

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