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Dive into the research topics where Muriel Gaubin is active.

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Featured researches published by Muriel Gaubin.


DNA and Cell Biology | 2003

Processing of filamentous bacteriophage virions in antigen-presenting cells targets both HLA class I and class II peptide loading compartments

Muriel Gaubin; Cristina Fanutti; Zohar Mishal; Antoine Durrbach; Piergiuseppe De Berardinis; Rossella Sartorius; Giovanna Del Pozzo; John Guardiola; Richard N. Perham; Dominique Piatier-Tonneau

Virions of filamentous bacteriophage fd are capable of displaying multiple copies of peptide epitopes and generating powerful immune responses to them. To investigate the antigen processing mechanisms in human B cell lines used as antigen presenting cells, the major coat protein (pVIII) in intact virions was fluorescently labeled, and its localization in various intracellular compartments was followed using confocal microscopy. We show that the virions were taken up and processed to yield peptides that reach both the major histocompatibility complex (MHC) class II compartment and the endoplasmic reticulum. Moreover, when exposed to bacteriophages displaying a cytotoxic T lymphocyte (CTL) epitope from the reverse transcriptase of human immunodeficiency virus type-1 (HIV-1), B cells were lysed by specific cytotoxic lymphocytes. This confirms that filamentous bacteriophage virions are capable of being taken up and processed efficiently by MHC class I and class II pathways, even in nonprofessional antigen presenting cells. These remarkable features explain, at least in part, the unexpected ability of virions displaying foreign T-cell epitopes to prime strong T-helper-dependent CTL responses. These findings have important implications for the development of peptide-based vaccines, using filamentous bacteriophage virions as scaffolds.


Journal of Biological Chemistry | 1997

Transduction of Activation Signal That Follows HIV-1 Binding to CD4 and CD4 Dimerization Involves the Immunoglobulin CDR3-like Region in Domain 1 of CD4

Laurence Briant; Nathalie Signoret; Muriel Gaubin; Véronique Robert-Hebmann; Xin Zhang; Mark I. Greene; Dominique Piatier-Tonneau; Christian Devaux

The role of CD4 during the human immunodeficiency virus type 1 (HIV-1) life cycle in T cells is not restricted to binding functions. HIV-1 binding to CD4 also triggers signals that lead to nuclear translocation of NF-κB and are important to the productive infection process. In addition to its cytoplasmic tail, in the ectodomain, the immunoglobulin (Ig) CDR3-like region of CD4 domain 1 seemed to play a role in this cascade of signals. We demonstrate in this work that the structural integrity of the CDR3-like loop is required for signal transduction. Substitutions of negatively charged residues by positively charged residues within the CDR3-like loop either inhibited NF-κB translocation after HIV-1 and gp120-anti-gp120 immune complexes binding to E91K,E92K mutants or induced its constitutive activation for E87K,D88K mutants. Moreover, A2.01–3B cells expressing the E91K,E92K mutant exhibited a lower HIV-1Lai replication. These cells, however, expressed p56 lck , demonstrated NF-κB translocation upon PMA stimulation, bound HIV-1Lai envelope glycoprotein with high affinity, and contained HIV-1 DNA 24 h after exposure to virus. E91K, E92K, and E87K,D88K mutant CD4 molecules were unable to bind a CD4 synthetic aromatically modified exocyclic, CDR3.AME-(82–89), that mimics the CDR3-like loop structure and binds to native cell surface CD4. This result together with molecular modeling studies indicates that the CDR3.AME-(82–89) analog binds to the CDR3-like loop of CD4 and strongly suggests that this region represents a site for CD4 dimerization. The negative charges on the CDR3-like loop thus appear critical for CD4-mediated signal transduction most likely related to CD4 dimer formation.


Current HIV Research | 2003

Use of Fusion Proteins and Procaryotic Display Systems for Delivery of HIV-1 Antigens: Development of Novel Vaccines for HIV-1 Infection

Piergiuseppe De Berardinis; Rossella Sartorius; Antonella Caivano; Dina Mascolo; Gonzalo J. Domingo; Giovanna Del Pozzo; Muriel Gaubin; Richard N. Perham; Dominique Piatier-Tonneau; John Guardiola

Two non-pathogenic scaffolds (represented by the filamentous bacteriophage fd and the dihydrolipoyl acetyltransferase E2 protein of the Bacillus stearothermophilus pyruvate dehydrogenase (PDH) complex) able to deliver human immunodeficiency virus (HIV)-1 antigenic determinants, were designed in our laboratories and investigated in controlled assay conditions. Based on a modification of the phage display technology, we developed an innovative concept for a safe and inexpensive vaccine in which conserved antigenic determinants of HIV-1 reverse transcriptase (RTase) were inserted into the N-terminal region of the major pVIII coat protein of bacteriophagefd virions. Analogously, we developed another antigen delivery system based on the E2 component from the PDH complex and capable of displaying large intact proteins on the surface of an icosahedral lattice. Our data show that both of these systems can deliver B and T epitopes to their respective presentation compartments in target cells and trigger a humoral response as well as a potent helper and cytolytic response in vitro and in vivo.


Human Immunology | 1999

Definition of the α2 region of HLA-DR molecules involved in CD4 binding

Muriel Gaubin; Rémi Houlgatte; Monica Dettin; Claudia Scarinci; Michelle Martin; John Guardiola; Carlo Di Bello; Dominique Piatier-Tonneau

Abstract HLA class II molecules present antigenic peptides to the T cell receptor of CD4+ T lymphocytes and interact with CD4 during the antigen recognition process. A major CD4 binding site encompassing amino acids (aa) 134–148 in the β2 domain of HLA-DR has been previously identified and residues located within the α2 subunit of murine MHC class II I-A d molecules have been shown to contribute to CD4-class II interaction. To characterize the α2 region of HLA-DR molecules involved in the binding of CD4, we have synthesized overlapping linear and cyclic peptides derived from a region encompassing aa 121–143. We demonstrate that two linear peptides (aa 124–138 and 130–143) and a cyclic one (aa 121–138) specifically bind to CD4-sepharose affinity columns. Although cyclic analogues exhibit more ordered populations as detected by circular dichroism measurements, cyclization did not improve the activity of some peptides. Peptide sequence positioning in HLA-DR1 dimer model indicates that α2 residues 124 to 136 form a solvent-exposed loop which faces the β2 loop delimited by residues 134–148. These data suggest that one CD4 molecule contacts both α2 and β2 loops of the HLA-DR homodimer.


Journal of Immunology | 1999

Potent Inhibition of CD4/TCR-Mediated T Cell Apoptosis by a CD4-Binding Glycoprotein Secreted from Breast Tumor and Seminal Vesicle Cells

Muriel Gaubin; Monica Autiero; Stéphane Basmaciogullari; Didier Métivier; Zohar Misëhal; Raphal Culerrier; Anne Oudin; John Guardiola; Dominique Piatier-Tonneau


Nature Biotechnology | 1997

Synthetic CD4 exocyclics inhibit binding of human immunodeficiency virus type 1 envelope to CD4 and virus replication in T lymphocytes

Xin Zhang; Muriel Gaubin; Laurence Briant; Vasantha Srikantan; Uri Saragovi; David B. Weiner; Christian Devaux; Monica Autiero; Dominique Piatier-Tonneau; Mark I. Greene


FEBS Journal | 1997

Surface Plasmon Resonance Analysis of gp17, a Natural CD4 Ligand from Human Seminal Plasma Inhibiting Human Immunodeficiency Virus Type-1 gp120-Mediated Syncytium Formation

Monica Autiero; Muriel Gaubin; Jean-Claude Mani; Christophe Castejon; Michelle Martin; Sandrine El Marhomy; John Guardiola; Dominique Piatier-Tonneau


Biochemistry | 2000

Mapping the CD4 binding domain of gp17, a glycoprotein secreted from seminal vesicles and breast carcinomas.

Stéphane Basmaciogullari; Monica Autiero; Raphaël Culerrier; Jean-Claude Mani; Muriel Gaubin; Zohar Mishal; John Guardiola; Claude Granier; Dominique Piatier-Tonneau


DNA and Cell Biology | 1999

Abnormal restriction pattern of PIP gene associated with human primary prostate cancers.

Monica Autiero; Raphael Culerrier; Christiane Bouchier; Stéphane Basmaciogullari; Muriel Gaubin; Sandrine El Marhomy; Pascal Blanchet; V. Paradis; Alain Jardin; John Guardiola; Dominique Piatier-Tonneau


Experimental and Molecular Pathology | 2002

Study of Disabling T-Cell Activation and Inhibiting T-Cell-Mediated Immunopathology Reveals a Possible Inverse Agonist Activity of CD4 Peptidomimetics

Takeo Horie; Yuan Shen; Kiichi Kajino; Muriel Gaubin; Giovanna Bonomi; Jean-Claude Mani; Alan Berezov; Dominique Piatier-Tonneau; John Guardiola; Brendan Hillard; Abdolmohamad Rostami; Mark I. Greene

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Dominique Piatier-Tonneau

Centre national de la recherche scientifique

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Monica Autiero

Centre national de la recherche scientifique

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Michelle Martin

Centre national de la recherche scientifique

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Stéphane Basmaciogullari

Centre national de la recherche scientifique

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Mark I. Greene

University of Pennsylvania

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Christian Devaux

Centre national de la recherche scientifique

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Jean-Claude Mani

Centre national de la recherche scientifique

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Rémi Houlgatte

Centre national de la recherche scientifique

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Sandrine El Marhomy

Centre national de la recherche scientifique

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