Ronald N. Germain

Key Role of Local Regulation in Chemosensing Revealed by a New Molecular Interaction-Based Modeling Method (2006)

Martin Meier-Schellersheim, Xuehua Xu, Bastian Angermann, Eric J. Kunkel, Tian Jin, Ronald N. Germain

The signaling network underlying eukaryotic chemosensing is a complex combination of receptor-mediated transmembrane signals, lipid modifications, protein translocations, and differential...

Key role of local regulation in chemosensing revealed by a new molecular interaction-based modeling method (2006)

Martin Meier-Schellersheim, Xuehua Xu, Bastian R Angermann, Erik J Kunkel, Tian Jin, Ronald N Germain

The signaling network underlying eukaryotic chemosensing is a complex combination of receptor-mediated transmembrane signals, lipid modifications, protein translocations, and differential...

Modeling T Cell Antigen Discrimination Based on Feedback Control of Digital ERK Responses (2005)

Grégoire Altan-Bonnet, Ronald N. Germain

Computational modeling provide a model which accounts for the high sensitivity, ligand selectivity, and low noise in TCR signaling. Several predictions of the model are supported by experimental data.

Modeling T Cell Antigen Discrimination Based on Feedback Control of Digital ERK Responses (2005)

Grégoire Altan-Bonnet, Ronald N. Germain

T-lymphocyte activation displays a remarkable combination of speed, sensitivity, and discrimination in response to peptide–major histocompatibility complex (pMHC) ligand engagement of clonally...

Comparison of thymocyte development in normal and invariant chain-deficient mice provides evidence that maturation-related changes in TCR and co-receptor levels play a critical role in cell fate (1996)

Huang, Li-Yun, Bikoff, Elizabeth K., Germain, Ronald N., MacDonald, H. R

Cells of Invariant chain-deficient mice show a substantial decrease in cell surface MHC class II protein expression, as well as a change In the occupancy of the expressed class II molecules. Taking...

Direct delivery of exogenous MHC class I molecule-binding oligopeptides to the endoplasmic reticulum of viable cells

Day, Patricia M., Yewdell, Jonathan W., Porgador, Angel, Germain, Ronald N., Bennink, Jack R.

After brief incubation of cells with fluorescein-conjugated peptides that bind major histocompatibility complex (MHC) class I molecules, peptides were detected within the endoplasmic reticulum (ER)...

Production, specificity, and functionality of monoclonal antibodies to specific peptide–major histocompatibility complex class II complexes formed by processing of exogenous protein

Zhong, Guangming, E Sousa, Caetano Reis, Germain, Ronald N.

Several unanswered questions in T cell immunobiology relating to intracellular processing or in vivo antigen presentation could be approached if convenient, specific, and sensitive reagents were...

Modeling T Cell Antigen Discrimination Based on Feedback Control of Digital ERK Responses

Altan-Bonnet, Grégoire, Germain, Ronald N

T-lymphocyte activation displays a remarkable combination of speed, sensitivity, and discrimination in response to peptide–major histocompatibility complex (pMHC) ligand engagement of clonally...

Decreased CD4 expression by polarized T helper 2 cells contributes to suboptimal TCR-induced phosphorylation and reduced Ca2+ signaling

Itoh, Yasushi, Wang, Ze, Ishida, Hideaki, Eichelberg, Katrin, Fujimoto, Noriki, Makino, Jin, ...

Polarized Th1 and Th2 cells expressing the same TCR produce distinct biochemical responses to ligand engagement. Compared to Th1 cells, Th2 cells show altered substrate tyrosine phosphorylation and a...

An extended vision for dynamic high-resolution intravital immune imaging

Germain, Ronald N., Castellino, Flora, Chieppa, Marcello, Egen, Jackson G., Huang, Alex Y.C., Koo, Lily Y., ...

The past few years have seen the application of confocal and especially two-photon microscopy to the dynamic high-resolution imaging of lymphocytes and antigen presenting cells within organs such as...

Key Role of Local Regulation in Chemosensing Revealed by a New Molecular Interaction-Based Modeling Method

Meier-Schellersheim, Martin, Xu, Xuehua, Angermann, Bastian, Kunkel, Eric J, Jin, Tian, Germain, Ronald N

The signaling network underlying eukaryotic chemosensing is a complex combination of receptor-mediated transmembrane signals, lipid modifications, protein translocations, and differential...

Direct delivery of exogenous MHC class I molecule-binding oligopeptides to the endoplasmic reticulum of viable cells

Day, Patricia M., Yewdell, Jonathan W., Porgador, Angel, Germain, Ronald N., Bennink, Jack R.

After brief incubation of cells with fluorescein-conjugated peptides that bind major histocompatibility complex (MHC) class I molecules, peptides were detected within the endoplasmic reticulum (ER)...

Production, specificity, and functionality of monoclonal antibodies to specific peptide–major histocompatibility complex class II complexes formed by processing of exogenous protein

Zhong, Guangming, E Sousa, Caetano Reis, Germain, Ronald N.

Several unanswered questions in T cell immunobiology relating to intracellular processing or in vivo antigen presentation could be approached if convenient, specific, and sensitive reagents were...

Modeling T Cell Antigen Discrimination Based on Feedback Control of Digital ERK Responses

Altan-Bonnet, Grégoire, Germain, Ronald N

T-lymphocyte activation displays a remarkable combination of speed, sensitivity, and discrimination in response to peptide–major histocompatibility complex (pMHC) ligand engagement of clonally...

Key Role of Local Regulation in Chemosensing Revealed by a New Molecular Interaction-Based Modeling Method

Meier-Schellersheim, Martin, Xu, Xuehua, Angermann, Bastian, Kunkel, Eric J, Jin, Tian, Germain, Ronald N

The signaling network underlying eukaryotic chemosensing is a complex combination of receptor-mediated transmembrane signals, lipid modifications, protein translocations, and differential...

Dynamic imaging of dendritic cell extension into the small bowel lumen in response to epithelial cell TLR engagement

Chieppa, Marcello, Rescigno, Maria, Huang, Alex Y.C., Germain, Ronald N.

Cells lining the gastrointestinal tract serve as both a barrier to and a pathway for infectious agent entry. Dendritic cells (DCs) present in the lamina propria under the columnar villus epithelium...

Natural killer cell behavior in lymph nodes revealed by static and real-time imaging

Bajénoff, Marc, Breart, Béatrice, Huang, Alex Y.C., Qi, Hai, Cazareth, Julie, Braud, Veronique M., ...

Natural killer (NK) cells promote dendritic cell (DC) maturation and influence T cell differentiation in vitro. To better understand the nature of the putative interactions among these cells in vivo...

Constitutive Presentation of a Natural Tissue Autoantigen Exclusively by Dendritic Cells in the Draining Lymph Node

Scheinecker, Clemens, McHugh, Rebecca, Shevach, Ethan M., Germain, Ronald N.

The major histocompatibility complex (MHC)-dependent presentation of processed tissue-specific self-antigens can contribute to either peripheral (extrathymic) tolerance or the differentiation of...

The Formation of Immunogenic Major Histocompatibility Complex Class II–Peptide Ligands in Lysosomal Compartments of Dendritic Cells Is Regulated by Inflammatory Stimuli

Inaba, Kayo, Turley, Shannon, Iyoda, Tomonori, Yamaide, Fumiya, Shimoyama, Susumu, E Sousa, Caetano Reis, ...

During their final differentiation or maturation, dendritic cells (DCs) redistribute their major histocompatibility complex (MHC) class II products from intracellular compartments to the plasma...

Related Leucine-based Cytoplasmic Targeting Signals in Invariant Chain and Major Histocompatibility Complex Class II Molecules Control Endocytic Presentation of Distinct Determinants in a Single Protein

Zhong, Guangming, Romagnoli, Paola, Germain, Ronald N.

Leucine-based signals in the cytoplasmic tail of invariant chain (Ii) control targeting of newly synthesized major histocompatibility complex class II molecules to the endocytic pathway for...

Quantitative Impact of Thymic Clonal Deletion on the T Cell Repertoire

Marguerat, Samuel, Lees, Rosemary K., Germain, Ronald N., Fowlkes, B.J., MacDonald, H. Robson

Interactions between major histocompatibility complex (MHC) molecules expressed on stromal cells and antigen-specific receptors on T cells shape the repertoire of mature T lymphocytes emerging from...

The Efficiency of CD4 Recruitment to Ligand-engaged TCR Controls the Agonist/Partial Agonist Properties of Peptide–MHC Molecule Ligands

Madrenas, Joaquín, Chau, Luan A., Smith, Judy, Bluestone, Jeffrey A., Germain, Ronald N.

One hypothesis seeking to explain the signaling and biological properties of T cell receptor for antigen (TCR) partial agonists and antagonists is the coreceptor density/kinetic model, which proposes...

Single Cell Analysis Reveals Regulated Hierarchical T Cell Antigen Receptor Signaling Thresholds and Intraclonal Heterogeneity for Individual Cytokine Responses of CD4+ T Cells

Itoh, Yasushi, Germain, Ronald N.

T cell receptor (TCR) recognition of peptide–major histocompatibility complex antigens can elicit a diverse array of effector activities. Here we simultaneously analyze TCR engagement and the...

Antigen-unspecific B Cells and Lymphoid Dendritic Cells Both Show Extensive Surface Expression of Processed Antigen–Major Histocompatibility Complex Class II Complexes after Soluble Protein Exposure In Vivo or In Vitro

Zhong, Guangming, Sousa, Caetano Reis E, Germain, Ronald N.

Intravenous (i.v.) injection of high amounts of soluble proteins often results in the induction of antigen-specific tolerance or deviation to helper rather than inflammatory T cell immunity. It has...

In Vivo Microbial Stimulation Induces Rapid CD40 Ligand–independent Production of Interleukin 12 by Dendritic Cells and their Redistribution to T Cell Areas

Sousa, Caetano Reis E, Hieny, Sara, Scharton-Kersten, Tanya, Jankovic, Dragana, Charest, Hugues, Germain, Ronald N., ...

The early induction of interleukin (IL)-12 is a critical event in determining the development of both innate resistance and adaptive immunity to many intracellular pathogens. Previous in vitro...

Selective Induction of Apoptosis in Mature T Lymphocytes by Variant T Cell Receptor Ligands

Combadière, Behazine, E Sousa, Caetano Reis, Germain, Ronald N., Lenardo, Michael J.

Activation, anergy, and apoptosis are all possible outcomes of T cell receptor (TCR) engagement. The first leads to proliferation and effector function, whereas the others can lead to partial or...

Predominant Role for Directly Transfected Dendritic Cells in Antigen Presentation to CD8+ T Cells after Gene Gun Immunization

Porgador, Angel, Irvine, Kari R., Iwasaki, Akiko, Barber, Brian H., Restifo, Nicholas P., Germain, Ronald N.

Cutaneous gene (DNA) bombardment results in substantial expression of the encoded antigen in the epidermal layer as well as detectable expression in dendritic cells (DC) in draining lymph nodes...

Receptor-Mediated Uptake of Antigen/Heat Shock Protein Complexes Results in Major Histocompatibility Complex Class I Antigen Presentation via Two Distinct Processing Pathways

Castellino, Flora, Boucher, Philip E., Eichelberg, Katrin, Mayhew, Mark, Rothman, James E., Houghton, Alan N., ...

Heat shock proteins (HSPs) derived from tumors or virally infected cells can stimulate antigen-specific CD8+ T cell responses in vitro and in vivo. Although this antigenicity is known to arise from...

Special regulatory T-cell review: A rose by any other name: from suppressor T cells to Tregs, approbation to unbridled enthusiasm

Germain, Ronald N

In the early 1970s a spate of papers by research groups around the world provided evidence for a negative regulatory role of thymus-derived lymphocytes (T cells). In 1971, Gershon and Kondo published...

Visualization and Identification of IL-7 Producing Cells in Reporter Mice

Mazzucchelli, Renata I., Warming, Søren, Lawrence, Scott M., Ishii, Masaru, Abshari, Mehrnoosh, Washington, A. Valance, ...

Interleukin-7 (IL-7) is required for lymphocyte development and homeostasis although the actual sites of IL-7 production have never been clearly identified. We produced a bacterial artificial...