A5079424748- Immune Cell Function and Interaction
- T-cell and B-cell Immunology
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Viral-associated cancers and disorders
- Cancer Cells and Metastasis
- Lymphoma Diagnosis and Treatment
- Hematopoietic Stem Cell Transplantation
- IL-33, ST2, and ILC Pathways
- Cancer Immunotherapy and Biomarkers
- Cytomegalovirus and herpesvirus research
- Glycosylation and Glycoproteins Research
- Monoclonal and Polyclonal Antibodies Research
- Eosinophilic Disorders and Syndromes
- Cell Adhesion Molecules Research
- Reproductive System and Pregnancy
- Cytokine Signaling Pathways and Interactions
- Immune Response and Inflammation
- Antimicrobial Resistance in Staphylococcus
- Infective Endocarditis Diagnosis and Management
- Adenosine and Purinergic Signaling
- Chemokine receptors and signaling
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Calcium signaling and nucleotide metabolism
- Autophagy in Disease and Therapy
University of Wisconsin–Madison
2013-2024
University of Wisconsin System
2021-2024
University of Wisconsin Carbone Cancer Center
2022-2023
W. M. Keck Foundation
2012
Harvard University
2002-2005
Brigham and Women's Hospital
2000-2004
Harvard University Press
2000-2004
University of New Hampshire
2004
University of Birmingham
2004
Albert Einstein College of Medicine
2004
CD1d-restricted natural killer (NK)T cells are known to potently secrete T helper (Th)1 and Th2 cytokines mediate cytolysis, but it is unclear how these contrasting functional activities regulated. Using lipid antigen–loaded CD1d tetramers, we have distinguished two subsets of in fresh peripheral blood that differ cytokine production cytotoxic activation. One subset, which was CD4−, selectively produced the Th1 interferon γ tumor necrosis factor α, expressed NKG2d, a marker associated with...
Although inhibition of natural killer (NK) cell-mediated lysis by the class I HLA molecules target cells is an established phenomenon, knowledge features which induce this effect remains rudimentary. Using alleles HLA-B*1502 and B*1513 differ only at residues 77-83 define Bw4 Bw6 serological epitopes, we tested hypothesis that presence epitope on determines recognition NKB1+ NK cells. HLA-B*1513 possesses epitope, whereas B*1502 has epitope. Lysis cell clones transfected expressing as HLA-A,...
Abstract Cytotoxicity of human NK cells is under negative control killer cell Ig-like receptors (KIR) specific for HLA class I. To determine the specificity five KIR containing two Ig domains (KIR2D), direct binding soluble recombinant KIR2D to a panel I transfectants was assayed. One KIR2D, derived from an inhibitory receptor with long cytoplasmic tail (KIR2DL1), bound HLA-C allotypes asparagine 77 and lysine 80 in heavy chain, as expected, since these inhibit lysis by expressing KIR2DL1....
Epstein-Barr virus (EBV) infects cells in latent or lytic forms, but the role of infection EBV-induced lymphomas is unclear. Here, we have used a new humanized mouse model, which both human fetal CD34(+) hematopoietic stem and thymus/liver tissue are transplanted, to compare EBV pathogenesis lymphoma formation following with replication-defective BZLF1-deleted (Z-KO) lytically active BZLF1(+) control. Both control Z-KO viruses established long-term viral latency all infected animals. The...
Natural killer (NK) cells kill normal and transformed hematopoietic that lack expression of major histocompatibility complex (MHC) class I antigens. Lysis HLA-negative Epstein Barr virus-transformed B lymphoblastoid cell lines (B-LCL) by human NK clones can be inhibited transfection the target with certain HLA-A, -B, or -C alleles. established from an individual demonstrate clonal heterogeneity in HLA recognition a single clone recognize multiple We describe potential receptor (NKB1) for...
Bacterial superantigens bind with high affinity to major histocompatibility complex (MHC) class II antigens on antigen-presenting cells and T cell antigen receptor (TCR) β chains lymphocytes, which results in the activation responsible for toxic shock syndrome food poisoning. Many cytotoxic lymphocyte (CTL) clones were shown have receptors human leukocyte (HLA) I molecules that inhibited superantigen-induced cytotoxicity against appropriate I-bearing target cells. One type of inhibitory...
Natural killer T (NKT) cells are a subset of lymphocytes with potent immunoregulatory properties. Recognition self-antigens presented by CD1d molecules is an important route NKT cell activation; however, the molecular identity specific autoantigens that stimulate human remains unclear. Here, we have analyzed recognition cellular ligands. The most clearly antigenic species was lyso-phosphatidylcholine (LPC). Diacylated phosphatidylcholine and lyso-phosphoglycerols differing in chemistry head...
Abstract CD1d-restricted T cells (NKT cells) are innate memory activated by lipid Ags and play important roles in the initiation regulation of immune response. However, little is known about trafficking patterns these or tissue compartment which they exert their regulatory activity. In this study, we determined chemokine receptor profile expressed found peripheral blood healthy volunteers as well cell clones. were identified Abs recognizing invariant Vα24 TCR rearrangement binding to CD1d-Fc...
Prior studies using polyclonal populations of natural killer (NK) cells have revealed that expression certain major histocompatibility complex (MHC) class I molecules on the membrane normal and transformed hematopoietic target can prevent NK cell-mediated cytotoxicity. However, extent clonal heterogeneity within cell population effect self versus non-self MHC alleles has not been clearly established. In present study, we generated more than 200 independently derived human clones from four...
CD1 molecules are glycoproteins that present lipid antigens at the cell surface for immunological recognition by specialized populations of T lymphocytes. Prior experimental data suggest a wide variety species can bind to molecules, but little is known about characteristics cellular ligands selected presentation. Here we have molecularly characterized lipids bound human CD1d isoform. Ligands were eluted from secreted and separated normal phase HPLC, then mass spectroscopy. A total 177...
ABSTRACT Immunosuppressed patients are at risk for developing Epstein-Barr Virus (EBV)-positive lymphomas that express the major EBV oncoprotein, LMP1. Although increasing evidence suggests a small number of lytically infected cells may promote EBV-positive lymphomas, impact enhanced lytic gene expression on ability to induce is unclear. Here we have used immune-deficient mice, engrafted with human fetal hematopoietic stem and thymus liver tissue, compare lymphoma formation following...
Epstein-Barr virus (EBV) infection causes B cell lymphomas in humanized mouse models and contributes to a variety of different types human lymphomas. T cells directed against viral antigens play critical role controlling EBV infection, EBV-positive are particularly common immunocompromised hosts. We previously showed that induces with high frequency cord blood-humanized model which EBV-infected blood is injected intraperitoneally into NOD/LtSz-scid/IL2Rγnull (NSG) mice. Since our former...
Allotypes from four divergent HLA-B families (B8, B15, B16, and B27) were compared for their inhibition of cytolysis by NK cells expressing the NKB1 receptor. differing solely at Bw4/Bw6 region examined as a more subset B15 allotypes. The capacity to interact with correlated precisely possession Bw4 sequence motif residues 77-83, whereas no correlation was made peptide-binding specificities two Bw6 allotypes family. having different motifs all NKB1. In contrast, HLA-A allotypes, which have...
In comparison with HLA-A and -B, the protein products of HLA-C locus are poorly characterized, in part because their low level expression at cell surface. Here, we examine how protein-protein interactions during assembly regulation mRNA affect surface HLA-C. We find that intrinsic properties heavy chain proteins do not correlate expression: chains associate dissociate beta 2-microglobulin (beta 2m) rates comparable to those found for increased competition 2m does alter From studies chimeric...
Although CD1d‐restricted NKT cells have been implicated as a participant in the regulatory mechanism of autoimmune diseases, it remains unclear how they would regulate human diseases such multiple sclerosis (MS). Furthermore, although comprise CD4+ and CD4– populations, prior studies often represented them simply population. Given that may represent functionally distinct appears crucial to examine individual subset diseases. Here we studied frequency cytokine phenotypes fresh peripheral...
Little is known about the role of CD1d-restricted T cells in antiviral immune responses. Here we show that lytic replication cycle Kaposi sarcoma–associated herpesvirus (KSHV) promotes downregulation cell-surface CD1d. This caused by expression 2 modulator recognition (MIR) proteins virus, each which loss surface CD1d following transfection into uninfected cells. Inhibition due to ubiquitination α-chain on a unique lysine residue its cytoplasmic tail, triggers endocytosis. Unlike...
Natural killer (NK) cells that express the NKB1 receptor are inhibited from killing target possess human histocompatibility leukocyte antigen (HLA) B molecules bearing Bw4 serological epitope. To investigate whether expression is affected by HLA type, peripheral blood lymphocytes of 203 HLA-typed donors were examined. Most had a single population NKB1+ cells, but some two populations expressing different cell surface levels NKB1, and others no detectable cells. Among both relative abundance...
Little is known about the role of CD1d-restricted T cells in antiviral immune responses. Here we show that lytic replication cycle Kaposi sarcoma–associated herpesvirus (KSHV) promotes downregulation cell-surface CD1d. This caused by expression 2 modulator recognition (MIR) proteins virus, each which loss surface CD1d following transfection into uninfected cells. Inhibition due to ubiquitination α-chain on a unique lysine residue its cytoplasmic tail, triggers endocytosis. Unlike...