Randy R. Brutkiewicz

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Albert Bendelac32
Luc Van Kaer28
Mitchell Kronenberg27
Mark H. Kaplan26
Steven P. Balk24
28Tonya J Roberts Webb
22Gourapura J. Renukaradhya
21Janice S. Blum
20Mitchell Kronenberg
19Venkataraman Sriram

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1985
2017
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Natural ligand of mouse CD1d1: cellular glycosylphosphatidylinositol.
Mouse CD1d1, a member of the CD1 family of evolutionarily conserved major histocompatibility antigen-like molecules, controls the differentiation and function of a T lymphocyte subset, NK1+ natural T cells, proposed to regulate immune responses. The CD1d1 crystal structure revealed a large hydrophobic binding site occupied by a ligand of unknown chemical… (More)
CD1 recognition by mouse NK1+ T lymphocytes.
Rare major histocompatibility complex (MHC) class I-like CD1-specific T cells have been isolated from human blood, but it has not been determined whether these clones are part of a defined subset of CD1-specific T cells selected during T cell development, or whether their recognition of CD1 is a fortuitous cross-reaction. In mice, an entire subset of alpha… (More)
CD1d1-dependent control of the magnitude of an acute antiviral immune response.
CD1d1-restricted NK T (NKT) cells rapidly secrete both Th1 and Th2 cytokines upon activation and are therefore thought to play a regulatory role during an immune response. In this study we examined the role of CD1d1 molecules and NKT cells in regulating virus-induced cytokine production. CD1d1-deficient (CD1KO) mice, which lack NKT cells, were infected with… (More)
Importance of N-linked glycosylation in the functional expression of murine CD1d1.
The mouse CD1d1 glycoprotein is specialized in presenting lipid antigens to a novel class of T cells called natural killer T (NKT) cells. CD1d1 is predicted to contain five potential N-linked glycosylation sites (asparagine residues at positions 25, 38, 60, 128, and 183). Glycosylation has been shown to invariably affect the molecular and functional… (More)
STAT3 promotes CD1d-mediated lipid antigen presentation by regulating a critical gene in glycosphingolipid biosynthesis.
Cytokines that regulate the immune response signal through the Janus kinase / signal transducer and activation of transcription (JAK/STAT) pathway, but whether this pathway can regulate CD1d-mediated lipid antigen presentation to natural killer T (NKT) cells is unknown. Here, we found that STAT3 promotes antigen presentation by CD1d. Antigen-presenting… (More)
Impaired assembly yet normal trafficking of MHC class I molecules in Tapasin mutant mice.
Loading of peptides onto major histocompatibility complex class I molecules involves a multifactorial complex that includes tapasin (TPN), a membrane protein that tethers empty class I glycoproteins to the transporter associated with antigen processing. To evaluate the in vivo role of TPN, we have generated Tpn mutant mice. In these animals, most class I… (More)
Cell wall glycosphingolipids of Sphingomonas paucimobilis are CD1d-specific ligands for NKT cells.
The current consensus on characterization of NKT cells is based on their reactivity to the synthetic glycolipid, alpha-galactosylceramide (alpha-GalCer) in a CD1d-dependent manner. Because of the limited availability of alpha-GalCer, there is a constant search for CD1d-presented ligands that activate NKT cells. The alpha-anomericity of the carbohydrate is… (More)
Defective presentation of the CD1d1-restricted natural Va14Ja18 NKT lymphocyte antigen caused by beta-D-glucosylceramide synthase deficiency.
Va14Ja18 natural T (NKT) cells play an immunoregulatory role, which is controlled by a self glycolipid(s) presented by CD1d. Although the synthetic antigen alpha-D-galactosylceramide (alpha-D-GalCer) stimulates all Va14Ja18 NKT cells, alpha-anomeric D-glycosylceramides are currently unknown in mammals. We have used beta-D-GalCer-deficient mice and… (More)
Heterosubtypic immunity to influenza A virus in mice lacking IgA, all Ig, NKT cells, or gamma delta T cells.
The mechanisms of broad cross-protection to influenza viruses of different subtypes, termed heterosubtypic immunity, remain incompletely understood. We used knockout mouse strains to examine the potential for heterosubtypic immunity in mice lacking IgA, all Ig and B cells, NKT cells (CD1 knockout mice), or gamma(delta) T cells. Mice were immunized with live… (More)
Lamp-2a facilitates MHC class II presentation of cytoplasmic antigens.
Extracellular antigens are internalized and processed before binding MHC class II molecules within endosomal and lysosomal compartments of professional antigen presenting cells (APC) for subsequent presentation to T cells. Yet select cytoplasmic peptides derived from autoantigens also intersect and bind class II molecules via an unknown mechanism. In human… (More)