Induced-self antigen

Induced-self antigen is a marker of abnormal self, which can be recognized upon infected (in particular, virus-infected) and transformed cells. Therefore, the recognition of "induced self" is an important strategy for surveillance of infection or tumor transformation - it results in elimination of the affected cells by activated NK cells or other immunological mechanisms.[1] Similarly γδ T cells can recognize induced-self antigens expressed on cells under stress conditions.[2]

Receptors

Probably the most studied receptor involved in recognition of induced-self antigens is NKG2D. It is an activating receptor which is expressed on NK cells and subsets of T and NKT cells. NKG2D can bind proteins at the surface of most cells that are not normally expressed, but that are expressed during a stress response of the cells (e.g. induction of the DNA damage pathway). Moreover, other recognition targets exist, for example ligands induced on human macrophages by TLR stimulation.[3] Ligands that bind to NKG2D receptor can be divided into two families of MHC class I-related proteins: MICs (MICA, MICB) and ULBPs (ULBP1, ULBP2, ULBP3, ULBP4, RAET1G, RAET1L).[4]

Other receptors able to bind induced-self antigens are NKG2C, NKG2E, NKG2F (CD94) or some NCRs (e.g. NKp 46 [5]).

Tumor targeting

Practical use of the knowledge of induced-self antigens is in targeting tumors for immune response. As tumors are very often capable of escaping the immune system by many ways, upregulation of specific ligands on the tumor cells could mount effective immune mechanisms able to eliminate these cells. For example, upregulation of NKG2D ligands can stimulate the NK cells triggering cell-mediated cytotoxicity.[6]

References
  1. Medzhitov, Ruslan; Charles A; Jr Janeway (2002-04-12). "Decoding the patterns of self and nonself by the innate immune system". Science. 296 (5566): 298–300. Bibcode:2002Sci...296..298M. CiteSeerX 10.1.1.134.9517. doi:10.1126/science.1068883. ISSN 1095-9203. PMID 11951031.
  2. Born, Willi K; M Kemal Aydintug; Rebecca L O'Brien (January 2013). "Diversity of γδ T-cell antigens". Cellular & Molecular Immunology. 10 (1): 13–20. doi:10.1038/cmi.2012.45. ISSN 2042-0226. PMC 4003174. PMID 23085946.
  3. Eissmann, Philipp; J Henry Evans; Maryam Mehrabi; Emma L Rose; Shlomo Nedvetzki; Daniel M Davis (2010-06-15). "Multiple mechanisms downstream of TLR-4 stimulation allow expression of NKG2D ligands to facilitate macrophage/NK cell crosstalk". Journal of Immunology. 184 (12): 6901–6909. doi:10.4049/jimmunol.0903985. ISSN 1550-6606. PMID 20488792.
  4. Fernández-Messina, Lola; Hugh T Reyburn; Mar Valés-Gómez (2012). "Human NKG2D-ligands: cell biology strategies to ensure immune recognition". Frontiers in Immunology. 3: 299. doi:10.3389/fimmu.2012.00299. ISSN 1664-3224. PMC 3457034. PMID 23056001.
  5. Arnon TI, Achdout H, Lieberman N, Gazit R, Gonen-Gross T, Katz G, Bar-Ilan A, Bloushtain N, Lev M, Joseph A, Kedar E, Porgador A, Mandelboim O (2004-01-15). "The mechanisms controlling the recognition of tumor- and virus-infected cells by NKp46". Blood. 103 (2): 664–672. doi:10.1182/blood-2003-05-1716. ISSN 0006-4971. PMID 14504081.
  6. Hayakawa, Yoshihiro (June 2012). "Targeting NKG2D in tumor surveillance". Expert Opinion on Therapeutic Targets. 16 (6): 587–599. doi:10.1517/14728222.2012.681378. ISSN 1744-7631. PMID 22530569.


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