Editing Antigen (section)

=== 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" />