ArticleJournal of immunology (Baltimore, Md. : 1950)2009
NK cell responsiveness is tuned commensurate with the number of inhibitory receptors for self-MHC class I: the rheostat model.
Article in Journal of immunology (Baltimore, Md. : 1950), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 149 papers.
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The trial behind it
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Who cites it
149 citing papers in PubMed, 271 citations in OpenAlex.
- Trial
- Follicular lymphoma patients with KIR2DL2 and KIR3DL1 and their ligands (HLA-C1 and HLA-Bw4) show improved outcome when receiving rituximab.Journal for immunotherapy of cancer · 2019Trial
- Long-term effect on natural killer cells by interferon-α therapy on the outcomes of HCV infection.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2014Trial
- ITPKB is a conserved regulator of natural killer cell desensitization/education that constrains antitumor immunity.bioRxiv : the preprint server for biology · 2026Article
- NKG2D upregulation sensitizes tumors to combined anti-PD1 and anti-VEGF therapy and prevents hearing loss.Nature communications · 2026Article
- Integrative Roles of NK Receptors and γδ TCRs in γδ T Cell-Mediated Cancer Immunity.Immune network · 2026Review
- Therapeutic reprogramming of natural killer cells for solid tumors: expanding frontiers into rare and ultra-rare malignancies.Frontiers in molecular biosciences · 2026Review
- Exceptional diversity of allorecognition receptors in a nonvertebrate chordate reveals principles of innate allelic discrimination.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Combined IFN-γ and TNF-α treatment enhances the susceptibility of breast cancer cells and spheroids to Natural Killer cell-mediated killing.Cell death & disease · 2025Article
- Chimeric antigen receptor natural killer (CAR-NK) cells: from preclinical promise to clinical reality in cancer immunotherapy.Immunotherapy · 2025Review
- Histocompatibility in Botryllus schlosseri and the origins of adaptive immunity.Immunogenetics · 2025Review
- Genotype-specific Expression of Uncle Fester Suggests a Role in Allorecognition Education in a Basal Chordate.Integrative and comparative biology · 2024Article
- Genetic and functional diversity of allorecognition receptors in the urochordate,bioRxiv : the preprint server for biology · 2024Article
- CAR-T and CAR-NK as cellular cancer immunotherapy for solid tumors.Cellular & molecular immunology · 2024Review
- HLA class I NK-epitopes and KIR diversities in patients with multiple myeloma.Immunogenetics · 2024Article
- Genotype-specific expression ofbioRxiv : the preprint server for biology · 2024Article
- Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation.Nature communications · 2023Article
- NK Cells in Cancer: Mechanisms of Dysfunction and Therapeutic Potential.International journal of molecular sciences · 2023Review
- Leukemia relapse via genetic immune escape after allogeneic hematopoietic cell transplantation.Research square · 2023Article
- Review
89 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
Abstract
Inhibitory receptors that engage self-MHC class I molecules enable NK cells to detect disease-associated loss of MHC class I on surrounding cells. Previous studies showed that some NK cells lack all receptors for self-MHC class I, yet fail to exhibit autoimmunity because they are generally hyporesponsive to stimulation. We asked whether NK cells exist in only two states, responsive and hyporesponsive, corresponding to cells that express or fail to express inhibitory receptors for self-MHC class I. The alternative model is that NK cells vary continuously in their responsiveness, based on variations in the number of different inhibitory and stimulatory receptors they express, which is known to vary. In this study, we show in the murine system that NK cell responsiveness increases quantitatively with each added self-MHC-specific inhibitory receptor. Genetic analysis demonstrated that interactions of each of the receptors with self-MHC class I were necessary to observe augmented responsiveness. These findings suggest that NK cell responsiveness is comparable to a rheostat: it is tuned to an optimal set point depending on the inhibitory and stimulatory interactions encountered in the normal environment, so as to ensure self-tolerance and yet optimize sensitivity to changes in normal cells.
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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.