Showing papers by "Mark M. Davis published in 2007"
TL;DR: It is shown that increasing miR-181a expression in mature T cells augments the sensitivity to peptide antigens, while inhibition in the immature T cells reduces sensitivity and impairs both positive and negative selection.
1,185 citations
TL;DR: Strong desensitization of diacylglycerol production, but not LAT phosphorylation, occurred shortly after TCR activation, suggesting that different molecular events play distinct signal-processing roles.
229 citations
TL;DR: In light of recent data showing that both helper and cytotoxic T cells can detect even a single molecule of an agonist peptide-MHC, alphabeta T cells are clearly a type of sensory cell, comparable to any in the nervous system, and can be considered as a sensory organ, trained on self-peptide- MHCs and primed to detect nonself.
Abstract: In light of recent data showing that both helper and cytotoxic T cells can detect even a single molecule of an agonist peptide-MHC, αβ T cells are clearly a type of sensory cell, comparable to any in the nervous system. In addition, endogenous (self ) peptides bound to MHCs are not just important for thymic selection, but also play an integral role in T cell activation in the response to foreign antigens. With the multitude of specificities available to most T cells, they can thus be considered as a sensory organ, trained on self-peptide-MHCs and primed to detect nonself.
145 citations
TL;DR: Biochemical analysis indicates that the pre-BCR is impaired in its ability to recognize antigen, which, together with electron microscopic visualization of a pre- BCR dimer, suggests ligand-independent oligomerization as the likely signaling mechanism.
Abstract: The pre-B cell receptor (pre-BCR) serves as a checkpoint in B cell development. In the 2.7 angstrom structure of a human pre-BCR Fab-like fragment, consisting of an antibody heavy chain (HC) paired with the surrogate light chain, the "unique regions" of VpreB and lambda5 replace the complementarity-determining region 3 (CDR3) loop of an antibody light chain and appear to "probe" the HC CDR3, potentially influencing the selection of the antibody repertoire. Biochemical analysis indicates that the pre-BCR is impaired in its ability to recognize antigen, which, together with electron microscopic visualization of a pre-BCR dimer, suggests ligand-independent oligomerization as the likely signaling mechanism.
115 citations
TL;DR: Mutagenesis is used to demonstrate that extracellular TCR-CD3 subunit interactions contribute to the structural integrity and function of this multisubunit receptor.
100 citations
TL;DR: Recent experimental data is highlighted that provides insights into the initiation of T-cell activation and the main controversies and uncertainties in this area are discussed.
56 citations
Patent•
24 Oct 2007TL;DR: The effects of microRNAs on antigen discrimination were in part achieved by dampening the expression of multiple negative regulators in the T cell receptor (TCR) signaling pathway as discussed by the authors.
Abstract: MicroRNAs (miRNAs) are a diverse and abundant class of ˜22-nucleotide (nt) endogenous regulatory RNAs that play a variety of roles in animal cells by controlling gene expression at the posttranscriptional level Increased miR-181a expression in mature T cells is shown to cause a marked increase in T cell activation and augments T cell sensitivity to peptide antigens Moreover, T cell blasts with higher miR-181a expression become reactive to antagonists The effects of miR-181a on antigen discrimination are in part achieved by dampening the expression of multiple negative regulators in the T cell receptor (TCR) signaling pathway, including PTPN22 and the dual specificity phosphatases DUSP5 and DUSP6 This results in a reduction in the TCR signaling threshold, thus quantitatively and qualitatively enhancing T cell sensitivity to antigens
21 citations
Patent•
24 Apr 2007TL;DR: In this article, the authors proposed a novel compositions of polymer-coated paramagnetic particles, defined as paramagnetic particle non-covalently coated with polymeric materials, which optionally possess targeting ligands, therapeutic agents, or carrier ligands.
Abstract: The present invention relates to novel compositions of polymer-coated paramagnetic particles, defined as paramagnetic particles non-covalently coated with polymeric materials, which optionally possess targeting ligands, therapeutic agents, or carrier ligands. By selecting from a variety of linker groups and targeting ligands the coated paramagnetic particles are suitable for a wide variety of methods for controlled delivery of the particles. The invention also relates to methods and uses of imaging, diagnosing, and treating diseased or cancerous tissue using the particles.
14 citations
TL;DR: Blimp-1 is a transcription factor that affects the expression of hundreds of genes in lymphocytes and its role in the maturation of B cells into immunoglobulin-secreting plasmablasts and in the control of T cell homeostasis and tolerance is confirmed.
Abstract: Blimp-1 is a transcription factor that affects the expression of hundreds of genes in lymphocytes Recent work confirmed its role in the maturation of B cells into immunoglobulin-secreting plasmablasts, as well as in the control of T cell homeostasis and tolerance What follows is a short history of how Blimp-1 was discovered
7 citations
TL;DR: Moon et al. as discussed by the authors reported the enumeration and isolation of naive CD4 + T cells and showed their numbers could predict the size and diversity of the primary immune response, but direct information has been elusive.
5 citations
Patent•
24 Oct 2007
TL;DR: In this paper, the microARN (miARN) constituent une classe diverse and abondante d'ARN regulateurs endogenes d'environ 22 nucleotides (nt) revetant une pluralite de fonctions dans les cellules animales par regulation de l'expression genetique au niveau post-transcriptionnel.
Abstract: Les microARN (miARN) constituent une classe diverse et abondante d'ARN regulateurs endogenes d'environ 22 nucleotides (nt) revetant une pluralite de fonctions dans les cellules animales par regulation de l'expression genetique au niveau post-transcriptionnel. On a observe que l'expression renforcee de miR-181a dans les lymphocytes T matures provoque une augmentation marquee de l'activation des lymphocytes T et augmente la sensibilite des lymphocytes T aux antigenes peptidiques. En outre, les lymphoblastes T presentant une expression de miR-181a plus elevee deviennent reactifs aux antagonistes. Les effets de miR-181a sur la discrimination antigenique sont en partie obtenus par attenuation de l'expression de multiples regulateurs negatifs dans la voie de signalisation des recepteurs des lymphocytes T (TCR), y compris PTPN22 et les phosphatases a double specificite DUSP5 et DUSP6. Il en resulte une reduction du seuil de signalisation des TCR, d'ou un renforcement quantitatif et qualitatif de la sensibilite des lymphocytes T aux antigenes.