- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- CAR-T cell therapy research
- Reproductive System and Pregnancy
- Hematopoietic Stem Cell Transplantation
- IL-33, ST2, and ILC Pathways
- Immunotherapy and Immune Responses
- Immune Response and Inflammation
- Cancer Immunotherapy and Biomarkers
- Cytomegalovirus and herpesvirus research
- Galectins and Cancer Biology
- Immune cells in cancer
- Mast cells and histamine
- Autoimmune and Inflammatory Disorders Research
- RNA Interference and Gene Delivery
- Single-cell and spatial transcriptomics
- Monoclonal and Polyclonal Antibodies Research
- Cutaneous lymphoproliferative disorders research
- Neuroinflammation and Neurodegeneration Mechanisms
- Transgenic Plants and Applications
- Toxin Mechanisms and Immunotoxins
- Celiac Disease Research and Management
- Fungal Infections and Studies
- Infections and bacterial resistance
- Carbohydrate Chemistry and Synthesis
Ospedale Policlinico San Martino
2023-2025
University of Genoa
2016-2025
Istituto Giannina Gaslini
2001-2004
Inserm
2001-2002
Assistance Publique – Hôpitaux de Paris
2001
Tecnologie Avanzate (Italy)
1996-1998
Alleanza Contro il Cancro
1993-1995
Universidad Autónoma de Madrid
1995
Catholic Biblical Association
1994
Istituto di Genomica Applicata
1994
Two major receptors involved in human natural cytotoxicity, NKp46 and NKp44, have recently been identified. However, experimental evidence suggested the existence of additional such receptor(s). In this study, by generation monoclonal antibodies (mAbs), we identified NKp30, a novel 30-kD triggering receptor selectively expressed all resting activated killer (NK) cells. Although mAb-mediated cross-linking NKp30 induces strong NK cell activation, masking inhibits cytotoxicity against normal or...
After culture in interleukin (IL)-2, natural killer (NK) cells acquire an increased capability of mediating non–major histocompatibility complex (MHC)–restricted tumor cell lysis. This may reflect, at least part, the de novo expression by NK triggering receptors involved cytolysis. In this study we identified a novel 44-kD surface molecule (NKp44) that is absent freshly isolated peripheral blood lymphocytes but progressively expressed all vitro after IL-2. Different from other markers...
Summary NKp46 has been shown to represent a novel, natural killer (NK) cell–specific surface molecule, involved in human NK cell activation. In this study, we further analyzed the role of cytotoxicity against different tumor target cells. We provide direct evidence that represents major activating receptor recognition and lysis both murine Although may cooperate with other receptors (including recently identified NKp44 molecule) induction NK-mediated cells, it only Molecular cloning cDNA...
Limited information is available on the surface molecules that are involved in natural killer (NK) cell triggering. In this study, we selected BAB281 monoclonal antibody (mAb) basis of its ability to trigger NK-mediated target lysis. identified a novel NK cell–specific molecule 46 kD (p46) expressed by all resting or activated cells. Importantly, unlike antigens so far, expression p46 was strictly confined Upon mAb-mediated cross-linking, induced strong triggering leading [Ca2+]i increases,...
The natural killer (NK) cell-specific p58 molecules EB6 and GL183 have been shown to represent the putative surface receptors for two distinct groups of human histocompatibility leukocyte antigen (HLA) C alleles. Interaction between class I expressed on target cells results in inhibition NK-mediated cytolytic activity thus cell protection. In present study, we show that may also act as mediating NK triggering. Activatory were found be confined only certain donors. Moreover, these donors, a...
Toll-like receptors (TLRs) are pattern-recognition responible for triggering cells of innate immunity. In this study we investigated the expression and function TLRs 3 9 in human natural killer (NK) cells. presence IL-12, freshly isolated NK responded to double-stranded RNA or unmethylated CpG DNA expressed CD69 CD25 activation markers. Because both markers were by virtually all cells, would suggest that most them can be triggered TLRs. Remarkably, cell stimulation also resulted induction...
NKp46 is a novel triggering receptor expressed by all human NK cells that involved in natural cytotoxicity. In this study we show the surface density of may vary different and precise correlation exists between phenotype clones their cytotoxicity against HLA-class I-unprotected allogeneic or xenogeneic cells. Thus, NKp46bright efficiently lysed murine tumor while NKp46dull were poorly cytolytic both types target We also correlates with ability to lyse autologous Finally, was found be deeply...
Abstract Natural killer (NK) cells are innate lymphoid (ILCs) contributing to immune responses microbes and tumors. Historically, their classification hinged on a limited array of surface protein markers. Here, we used single-cell RNA sequencing (scRNA-seq) cellular indexing transcriptomes epitopes by (CITE-seq) dissect the heterogeneity NK cells. We identified three prominent cell subsets in healthy human blood: NK1, NK2 NK3, further differentiated into six distinct subgroups. Our findings...
In humans, natural killer (NK) cell function is regulated by a series of receptors and coreceptors with either triggering or inhibitory activity. Here we describe novel 60-kD glycoprotein, termed NTB-A, that expressed all human NK, T, B lymphocytes. Monoclonal antibody (mAb)-mediated cross-linking NTB-A results in the induction NK-mediated cytotoxicity. Similar to 2B4 (CD244) functioning as coreceptor NK activation, also triggers cytolytic activity only cells expressing high surface...
Natural cytotoxicity receptors (NKp46, NKp44 and NKp30) play a predominant role in human NK cell triggering during natural cytotoxicity. Human 2B4 also induced activation redirected killing assays using anti-2B4 monoclonal antibodies (mAb) murine targets. Since this effect was confined to fraction of cells, suggested functional heterogeneity molecules. Here we show that via against targets is strictly dependent upon the engagement NKp46 by ligand (s) on target cells. Thus, clones expressing...
Celiac disease is a small intestine inflammatory disorder with multiple organ involvement, sustained by an inappropriate immune response to dietary gluten. Anti-transglutaminase antibodies are typical serological marker in patients active disease, and may disappear during gluten-free diet treatment. Involvement of infectious agents innate immunity has been suggested but never proven. Molecular mimicry one the mechanisms that links infection autoimmunity.In our attempt clarify pathogenesis...
In this study, by the generation of a specific monoclonal antibody, we identified p75/AIRM1 (for adhesion inhibitory receptor molecule 1), novel that is mostly confined to human natural killer cells. 75-kD glycoprotein that, upon sodium pervanadate treatment, becomes tyrosine phosphorylated and associates src homology 2 domain-bearing protein phosphatase (SHP)-1. The gene located on chromosome 19 encodes member sialoadhesin family characterized three immunoglobulin-like extracellular domains...
Abstract In an attempt to identify the amino acid position(s) of HLA‐C‐specific p58.1/p50.1 natural killer cell receptors that determine binding affinity for their ligand, we used soluble fusion proteins formed by ectodomain either receptor and Fc portion human IgG1. We show p50.1 (activating) binds weakly 221‐Cw4 transfectants. contrast, p58.1 (inhibitory) with high affinity. A single mutation at position 70, obtained site‐directed mutagenesis, was found affect both receptors. Thus,...
GL183 or EB6 (p58) molecules have been shown to function as receptors for different HLA-C alleles and deliver an inhibitory signal natural killer (NK) cells, thus preventing lysis of target cells. In this study, we analyzed a subset NK cells characterized by p58-negative surface phenotype. We show that clones, although specific class I do not recognize alleles. addition, the use appropriate transfected with HLA-class identified HLA-B7 protective element recognized fraction clones. attempt...
In this study we analyzed the progression of cell surface receptor expression during in vitro -induced human natural killer (NK) maturation from CD34 + Lin − precursors. NKp46 and NKp30, two major triggering receptors that play a central role cytotoxicity, were expressed before HLA class I-specific inhibitory receptors. Moreover, their appearance at correlated with acquisition cytolytic activity by developing NK cells. Although early may provide activating signals required for inducing...
Recent evidence has shown that CD56bright NK cells, a subset of cells abundant in lymph nodes, may have an immunoregulatory function. In multiple sclerosis (MS), expansion been associated to successful response different treatments and remission disease during pregnancy; how whether they exert immunoregulation physiologic conditions this is impaired MS not known. We dissected the role function healthy subjects (HS) compared it with untreated or patients clinically isolated syndrome...