ArticleThe Journal of clinical investigation2012
Human immunodeficiency-causing mutation defines CD16 in spontaneous NK cell cytotoxicity.
Article in The Journal of clinical investigation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.
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Who cites it
99 citing papers in PubMed, 1 synthesis or guideline pooled it, 156 citations in OpenAlex.
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- HSV-2 gE2/gI2 are immune evasion molecules that bind IgG Fc to inhibit antibody-dependent cellular cytotoxicity.Frontiers in immunology · 2026Article
- Insights into ectodomain shedding as a novel target in natural killer cell-based immunotherapy for cancer.Frontiers in immunology · 2026Review
- Engineered neutrophil engagers overcome IgA limitations and reprogram resting neutrophils for cancer immunotherapy.Journal of biological engineering · 2025Article
- The immune response to human cytomegalovirus: impact of age, co-morbidities and the significance of anti-viral activity assessment.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- CD16a pairs form the basal molecular subunit for the NK-cell ADCC lytic synapse.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
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- Complete CD16A Deficiency and Defective NK Cell Function in a Man Living with HIV.Journal of clinical immunology · 2025Article
- The FcγRIIIA (CD16) L48-H/R Polymorphism Enhances NK Cell-Mediated Antibody-Dependent Cellular Cytotoxicity by Promoting Serial Killing.Cancer immunology research · 2025Article
- The Golgi complex governs natural killer cell lytic granule positioning to promote directionality in cytotoxicity.Cell reports · 2025Article
- Generation and characterization of a tamoxifen-inducible lineage tracing toolFrontiers in immunology · 2025Article
- A potential prognostic marker for hematologic neoplasms: CD58.Frontiers in oncology · 2025Review
- Tissue-specific features of innate lymphoid cells in antiviral defense.Cellular & molecular immunology · 2024Review
- NK Cytotoxicity Mediated by NK-92 Cell Lines Expressing Combinations of Two Allelic Variants forAntibodies (Basel, Switzerland) · 2024Article
- MEF2C regulates NK cell effector functions through control of lipid metabolism.Nature immunology · 2024Article
- Functional genomics identifies N-acetyllactosamine extension of complex N-glycans as a mechanism to evade lysis by natural killer cells.Cell reports · 2024Article
39 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
The Fc receptor on NK cells, FcγRIIIA (CD16), has been extensively studied for its role in mediating antibody-dependent cellular cytotoxicity (ADCC). A homozygous missense mutation in CD16 (encoding a L66H substitution) is associated with severe herpesvirus infections in rare patients. Here, we identified a new patient with this CD16 mutation and compared the patient's NK cells to those of the originally reported patient. Patients with the L66H mutation had intact ADCC, but deficient spontaneous NK cell cytotoxicity and decreased surface expression of CD2, a coactivation receptor. Mechanistic studies in a human NK cell line, NK-92, demonstrated that CD16 expression correlated with CD2 surface levels and enabled killing of a melanoma cell line typically resistant to CD16-deficient NK-92 cells. An association between CD16 and CD2 was identified biochemically and at the immunological synapse, which elicited CD16 signaling after CD2 engagement. Stable expression of CD16 L66H in NK-92 cells recapitulated the patient phenotype, abrogating association of CD16 with CD2 as well as CD16 signaling after CD2 ligation. Thus, CD16 serves a role in NK cell-mediated spontaneous cytotoxicity through a specific association with CD2 and represents a potential mechanism underlying a human congenital immunodeficiency.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.