The DOI matches its Crossref record; 74 of the 78 references it cites were found in a registry or an index.
NKG2D Receptor and Its Ligands in Host Defense
Open accessAbstract
NKG2D is an activating receptor expressed on the surface of natural killer (NK) cells, CD8+ T cells, and subsets of CD4+ T cells, invariant NKT cells (iNKT), and γδ T cells. In humans, NKG2D transmits signals by its association with the DAP10 adapter subunit, and in mice alternatively spliced isoforms transmit signals either using DAP10 or DAP12 adapter subunits. Although NKG2D is encoded by a highly conserved gene (KLRK1) with limited polymorphism, the receptor recognizes an extensive repertoire of ligands, encoded by at least eight genes in humans (MICA, MICB, RAET1E, RAET1G, RAET1H, RAET1I, RAET1L, and RAET1N), some with extensive allelic polymorphism. Expression of the NKG2D ligands is tightly regulated at the level of transcription, translation, and posttranslation. In general, healthy adult tissues do not express NKG2D glycoproteins on the cell surface, but these ligands can be induced by hyperproliferation and transformation, as well as when cells are infected by pathogens. Thus, the NKG2D pathway serves as a mechanism for the immune system to detect and eliminate cells that have undergone “stress.” Viruses and tumor cells have devised numerous strategies to evade detection by the NKG2D surveillance system, and diversification of the NKG2D ligand genes likely has been driven by selective pressures imposed by pathogens. NKG2D provides an attractive target for therapeutics in the treatment of infectious diseases, cancer, and autoimmune diseases. Cancer Immunol Res; 3(6); 575–82. ©2015 AACR.
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“Remarkably, the candidate signature gene RAET1G is one of the few genes that could encode a ligand recognized by NKG2D proteins in response to stress and infections (Eagle and Trowsdale, 2007; Tomasec et al., 2007; Lanier, 2015).”
From Identification of Candidate Signature Genes and Key Regulators Associated With Trypanotolerance in the Sheko Breed (2019) · cites this paper as Lanier, 2015
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Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA.
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“Although NKG2D is expressed constitutively on essentially all resting human NK cells and CD8þ T cells (14), engagement of NKG2D alone is insufficient to trigger cell-mediated cytotoxicity or cytokine production (12, 40), although the simultaneous engagement of NKG2D and other "costimulatory" receptors, such as CD335 (…”
BackgroundSelf-citationTumour-derived soluble MIC ligands impair expression of NKG2D and T-cell activation
Groh, V., Wu, J. D., Yee, C., & Spies, T. (2002) · Nature · doi:10.1038/nature01112 · Cited by 1,674 · cited 1×
“These include systemic release of NKG2D ligands by tumors in cancer patients (65, 66).”
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“MICA, MICB, RAET1E (ULBP4), and RAET1G (ULBP5) are transmembrane-anchored glycoproteins, whereas RAET1I (ULBP1), RAET1H (ULBP2), RAET1N (ULBP3), and RAET1L (ULBP6) are glycophosphatidylinositol (GPI)-anchored, although RAET1H (ULBP2) may be expressed in both transmembraneanchored and GPI-anchored forms (28), and RAET1…”
BackgroundInfluentialThe DNA damage pathway regulates innate immune system ligands of the NKG2D receptor
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“In some cases, ligands may be induced due to the genomic instability of the transformed cells, resulting in activation of the ATM and ATR DNA repair pathways (61).”
BackgroundAn activating immunoreceptor complex formed by NKG2D and DAP10.
Wu, J., Song, Y., Bakker, A. B., Bauer, S., Spies, T., Lanier, L., & Phillips, J. (1999) · Science · doi:10.1126/science.285.5428.730 · Cited by 1,168 · cited 6×
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“Studies using transplantable mouse tumors have demonstrated that expression of an NKG2D ligand is sufficient to cause rejection of the tumor (62, 63).”
BackgroundImmunoreceptor DAP12 bearing a tyrosine-based activation motif is involved in activating NK cells
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“Association of NKG2D with DAP12 versus DAP10 has significant consequences for signal transduction in that DAP12 possesses a canonical immunotyrosine-based activation motif (ITAM), which recruits Syk and ZAP70 tyrosine kinases (7), whereas DAP10 has a YINM motif, which recruits a p85 PI3 kinase and Vav-1 signaling comp…”
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“Although NKG2D is expressed constitutively on essentially all resting human NK cells and CD8þ T cells (14), engagement of NKG2D alone is insufficient to trigger cell-mediated cytotoxicity or cytokine production (12, 40), although the simultaneous engagement of NKG2D and other "costimulatory" receptors, such as CD335 (…”
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Research works printed but not linked: 2
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Futas, J., Jelinek, A. L., Burger, P., & Hořín, P. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1459122
Characterisation of novel MICB alleles by next generation sequencing: MICB*055 and MICB*005:15
Shivarov, V., & Ivanova, M. (2024) · HLA · doi:10.1111/tan.15581
Si algo puede fallar, fallará: el virus Epstein-Barr y su contención inmunitaria
Gutiérrez-Guerrero, A., Espinosa-Padilla, S., Oswaldo, S., Lugo-Reyes, & Reyes, L. (2024) · Revista Alergia México · doi:10.29262/ram.v71i1.1276
Preclinical characterization of Pan-NKG2D ligand-binding NKG2D receptor decoys
Rupert, P. B., Buerger, M., Girard, E. J., Frutoso, M., Parrilla, D., Ng, K., Gooley, T. A., Groh, V., & Strong, R. K. (2024) · Heliyon · doi:10.1016/j.heliyon.2024.e28583
“Signaling through the NKG2D/NKG2D-L axis enables detection of viral infection or oncogenic transformation, with the presence of NKG2D-L associated with rejection of nascent tumors and viral clearance [1].”
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“MICA potential is one of the natural killer Group 2D (NKG2D) activation re - ceptor ligands, which promotes the activation of natural killer (NK) cells and leads to apoptosis of cells [13].”
BackgroundLis, N., Hein, Z., Ghanwat, S., Ramnarayan, V., Chambers, B., & Springer, S. (2020) · bioRxiv · doi:10.1101/2020.11.17.386763
“It is a stress ligand, a molecule that is not expressed in healthy cells of adults, but its expression can be triggered by viral infection or tumorigenesis (Cerwenka and Lanier, 2001; Lanier, 2015).”
BackgroundAssociation of Some NKG2 gene Family and it’ s Polymorphism with Pulmonary Tuberculosis
Al-Saad, N., Alsaadi, M., & Al-saadi, A. (2020) · Indian Journal of Forensic Medicine & Toxicology · doi:10.37506/ijfmt.v14i4.11785
“It is expressed by NK cells, γδ T cells and CD8+ αβ T cells [2].”
Dressel, R. (2017) · Transfusionsmedizin - Immunhämatologie Hämotherapie Immungenetik Zelltherapie · doi:10.1055/s-0043-113801
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“Ces ligands sont exprimés en condition de stress cellulaire, par exemple lors d’infections virales ou lors de transformations tumorales (Lanier, 2015).”
BackgroundRibeiro, L., Xavier, D. R., Rosa, T., Macêdo, A. A., Ribeiro, D. L. S., Paz, F. S., Silva, E. P., Ribeiro, A. I. L., Torres-Júnior, J. R. S., Viana, R. B., et al. (2025) · Brazilian journal of biology = Revista brasleira de biologia · doi:10.1590/1519-6984.281304
Li, X., Feng, S.-R., Wu, X.-Q., Liu, K., Liu, J., Lin, H., Lin, B., Li, W., Chen, Y., Pan, Y.-L., et al. (2025) · Cancer Advances · doi:10.53388/2025825022
“The cell membranes of numerous human tumors exhibited elevated expression of the stress protein MICB [2].”
Land, W. (2018) · Springer eBooks · doi:10.1007/978-3-319-78655-1_8
Activation and Function of Unconventional T Cells
Land, W. (2018) · Springer eBooks · doi:10.1007/978-3-319-78655-1_28
Activation and Function of Innate Lymphoid Cells
Land, W. G. (2018) · Springer eBooks · doi:10.1007/978-3-319-78655-1_27 · Cited by 1
Rotte, A., & Bhandaru, M. (2016) · Springer eBooks · doi:10.1007/978-3-319-48066-4_5
Metadata
- Authors
- Lanier, L. L.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Lanier, Lewis L.
- ORCID
- Lanier, Lewis L.
- Venue
- Cancer Immunology Research
- Published
- 2015-06-01
- Volume
- 3
- Issue
- 6
- Pages
- 575-582
- ISSN
- 2326-6066 (ISSN-L)
- 2326-6074
- PMC
- PMC4457299
- OpenAlex
- W2142548447
- Cited by
- 599
- References
- 78
- Citations by year
- 2026: 27 · 2025: 53 · 2024: 56 · 2023: 73 · 2022: 56 · 2021: 66 · 2020: 63 · 2019: 51 · 2018: 65 · 2017: 47 · 2016: 37 · 2015: 4
- FWCI
- 4.80
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Immunology Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Cancer Institute (R01CA089189)
- National Institute of Allergy and Infectious Diseases (AI-068129, R01AI068129, R37AI066897, AI066897)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
- Keywords
- NKG2D, NKG2D ligands, mica, MICB, natural killer cells, DAP10, DAP12, immune evasion, viral evasion, tumor immune evasion, host defense, NK cell activation
- MeSH terms
- Animals, Communicable Diseases, Humans, Killer Cells, Natural, Ligands, Lymphocyte Activation, Neoplasms, Lymphocyte Subsets, NK Cell Lectin-Like Receptor Subfamily K, Disease Resistance
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