ArticleJournal of immunology (Baltimore, Md. : 1950)2012
Mutation at positively selected positions in the binding site for HLA-C shows that KIR2DL1 is a more refined but less adaptable NK cell receptor than KIR2DL3.
Article in Journal of immunology (Baltimore, Md. : 1950), 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 84 citations in OpenAlex.
- Donor killer cell Ig-like receptor B haplotypes, recipient HLA-C1, and HLA-C mismatch enhance the clinical benefit of unrelated transplantation for acute myelogenous leukemia.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Protein language models accurately predict polymorphic peptide-modulated NK cell receptor-HLA class I interaction strengths.Science advances · 2026Article
- Molecular characterization of the archaic HLA-B∗73:01 allele reveals presentation of a unique peptidome and skewed engagement by KIR2DL2.The Journal of biological chemistry · 2025Article
- Article
- Donor KIR2DL1 Allelic Polymorphism Influences Posthematopoietic Progenitor Cell Transplantation Outcomes in the T Cell Depleted and Reduced Intensity Conditioning Setting.Transplantation and cellular therapy · 2024Article
- Allelic variation of KIR and HLA tunes the cytolytic payload and determines functional hierarchy of NK cell repertoires.Blood advances · 2023Article
- Immunogenomics of Killer Cell Immunoglobulin-Like Receptor (KIR) and HLA Class I: Coevolution and Consequences for Human Health.The journal of allergy and clinical immunology. In practice · 2022Article
- Individualized Constellation of Killer Cell Immunoglobulin-Like Receptors and Cognate HLA Class I Ligands that Controls Natural Killer Cell Antiviral Immunity Predisposes COVID-19.Frontiers in genetics · 2022Article
- Killer-cell immunoglobulin-like receptor/human leukocyte antigen-C combination and 'great obstetrical syndromes' (Review).Experimental and therapeutic medicine · 2021Review
- Following Transplantation for Acute Myelogenous Leukemia, DonorJournal of immunology (Baltimore, Md. : 1950) · 2021Article
- Structural plasticity of KIR2DL2 and KIR2DL3 enables altered docking geometries atop HLA-C.Nature communications · 2021Article
- Coexistence of inhibitory and activating killer-cell immunoglobulin-like receptors to the same cognate HLA-C2 and Bw4 ligands confer breast cancer risk.Scientific reports · 2021Article
- Regulation of MHC I Molecules in Glioblastoma Cells and the Sensitizing of NK Cells.Pharmaceuticals (Basel, Switzerland) · 2021Review
- High-Resolution Analysis Identifies High Frequency ofFrontiers in immunology · 2021Article
- High-Resolution Characterization ofFrontiers in immunology · 2021Article
- Hidden Patterns of Anti-HLA Class I Alloreactivity Revealed Through Machine Learning.Frontiers in immunology · 2021Article
- Article
- Tuning of human NK cells by endogenous HLA-C expression.Immunogenetics · 2020Review
- The Education of NK Cells Determines Their Responsiveness to Autologous HIV-Infected CD4 T Cells.Journal of virology · 2019Article
- Immunogenomic correlates of response to cetuximab monotherapy in head and neck squamous cell carcinoma.Head & neck · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Through recognition of HLA class I, killer cell Ig-like receptors (KIR) modulate NK cell functions in human immunity and reproduction. Although a minority of HLA-A and -B allotypes are KIR ligands, HLA-C allotypes dominate this regulation, because they all carry either the C1 epitope recognized by KIR2DL2/3 or the C2 epitope recognized by KIR2DL1. The C1 epitope and C1-specific KIR evolved first, followed several million years later by the C2 epitope and C2-specific KIR. Strong, varying selection pressure on NK cell functions drove the diversification and divergence of hominid KIR, with six positions in the HLA class I binding site of KIR being targets for positive diversifying selection. Introducing each naturally occurring residue at these positions into KIR2DL1 and KIR2DL3 produced 38 point mutants that were tested for binding to 95 HLA- A, -B, and -C allotypes. Modulating specificity for HLA-C is position 44, whereas positions 71 and 131 control cross-reactivity with HLA-A*11:02. Dominating avidity modulation is position 70, with lesser contributions from positions 68 and 182. KIR2DL3 has lower avidity and broader specificity than KIR2DL1. Mutation could increase the avidity and change the specificity of KIR2DL3, whereas KIR2DL1 specificity was resistant to mutation, and its avidity could only be lowered. The contrasting inflexibility of KIR2DL1 and adaptability of KIR2DL3 fit with C2-specific KIR having evolved from C1-specific KIR, and not vice versa. Substitutions restricted to activating KIR all reduced the avidity of KIR2DL1 and KIR2DL3, further evidence that activating KIR function often becomes subject to selective attenuation.
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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.