• complexes
  • The T cell antigen receptor (TCR) and pre-TCR complexes are composed of multiple signal-transducing subunits (CD3γ, CD3δ, CD3ε, and ζ) that each contain one or more copies of a semiconserved functional motif, the immunoreceptor tyrosine-based activation motif (ITAM). (rupress.org)
  • We revisited the issue of TCR valency by examining complexes isolated from primary αβ T cells after solubilization in digitonin. (jimmunol.org)
  • Therefore, we conclude that in primary T cells, TCR/CD3 complexes can be found that are physically and functionally bivalent. (jimmunol.org)
  • T cell Ag receptors are highly related to BCR in terms of evolutionary pedigree, gene structure, recombinase-dependent gene rearrangement during development, protein domain organization, and expression within multiprotein signaling complexes ( 1 ). (jimmunol.org)
  • The general format of the definitive IP experiment has been to examine T cells that express two different TCRs, allowing IP of one TCR to be followed by Western blotting for the second TCR to test for their inclusion in shared complexes. (jimmunol.org)
  • The Garcia Laboratory has also determined crystal structures of many other major cytokine-receptor complexes including those of IL-1, IL-4, IL-13, IL-15, IL-17, IL-23, LIF and CNTF. (wikipedia.org)
  • Garcia's group used directed evolution to strengthen low-affinity interactions between the receptor Notch1 and ligands Delta-like 4 (DLL4) and Jagged1 (Jag1) as a means of stabilizing the complexes for co-crystallization. (wikipedia.org)
  • In particular he has addressed the contribution of the T cell receptor (TCR) to recognition by T cells of peptide-MHC complexes by transfer of TCR alpha and beta genes from one T cell clone to another. (wikipedia.org)
  • Questions concerned with the role of positive and negative selection of developing T cells by peptide-MHC complexes in the thymus in generating an effective and self-tolerant immune system were analyzed in TCR transgenic mice. (wikipedia.org)
  • T helper (TH) cells, typically follicular T helper (TFH) cells, that were activated with the same antigen recognize and bind these MHC-II-peptide complexes through their T cell receptor (TCR). (wikipedia.org)
  • precursor
  • We have previously cloned the cDNA encoding murine CD27, prepared specific mAbs and observed that murine CD27 is expressed on virtually all thymocytes, with the exception of a subpopulation of CD4-8- precursor T cells. (rupress.org)
  • It is shown here that induction of murine CD27 expression occurs at the transition from the CD4-8-25+ to the CD4-8-25- precursor T cell stage and is regulated by the pre-TCR. (rupress.org)
  • Signaling by the TCR and its precursor, the pre-TCR, are also required for thymocyte development and selection ( 1 )( 2 )( 3 ). (rupress.org)
  • Previous studies on monocytic and colon cell lines suggest that plasmin pre-treatment can increase plasminogen binding, allowing the active enzyme to generate binding sites for its precursor. (biomedcentral.com)
  • Hematopoietic precursor cells isolated from patients on long-term suppressive HIV therapy did not contain HIV-1 DNA. (amfar.org)
  • estrogen recep
  • Studies in female mice have shown that estrogen receptor-alpha declines in the pre-optic hypothalamus as they grow old. (wikipedia.org)
  • At UC Berkeley, Timiras studied the effects of caloric restriction on various hypothalamic nuclei, specifically the effects on cell density, estrogen receptor alpha immunoreactivity and insulin-like growth factor-1 (IGF-1) receptor immunoreactivity. (wikipedia.org)
  • antibody
  • We investigated the structure of the pre-B cell receptor (preBCR) that plays a crucial role in the development and binding properties of an antibody. (oxy.edu)
  • March 2016 Clinical trial number NCT01351935 for "Escalating Dose Study in Subjects With Relapsed or Refractory B Cell Non-Hodgkin Lymphoma, Chronic Lymphocytic Leukemia, and Waldenstrom's Macroglobulinemia" at ClinicalTrials.gov BeiGene Announces Initiation of a Combination Trial of the BTK Inhibitor BGB-3111 with the PD-1 Antibody BGB-A317. (wikipedia.org)
  • Artemis plays an essential role in V(D)J recombination, the process by which B cell antibody genes and T cell receptor genes are assembled from individual V (variable), D (diversity), and J (joining) segments. (wikipedia.org)
  • The exact site of cleavage of the hairpin by Artemis is variable, and this variability, combined with random nucleotide deletion and addition, confers extreme diversity upon the resulting antibody and T-cell receptor genes, thus allowing the immune system to mount an immune response to virtually any foreign antigen. (wikipedia.org)
  • BCRs allow the B cell to bind to a specific antigen, against which it will initiate an antibody response. (wikipedia.org)
  • Signaling
  • Experimental data support the idea that at least some TCR-ITAMs are functionally equivalent with respect to the signaling requirements for T cell development. (rupress.org)
  • Required for TCR (T-cell antigen receptor)- and pre-TCR-mediated signaling, both in mature T-cells and during their development. (uniprot.org)
  • Couples activation of these receptors and their associated kinases with distal intracellular events such as mobilization of intracellular calcium stores, PKC activation, MAPK activation or cytoskeletal reorganization through the recruitment of PLCG1, GRB2, GRAP2, and other signaling molecules. (uniprot.org)
  • As a result, most paradigms of T cell activation predict that low-affinity binding of peptide/MHC (pMHC) to monovalent αβ TCR represents the decisive molecular event of Ag recognition, the initial interaction that culminates in TCR aggregation and T cell signaling ( 2 ). (jimmunol.org)
  • Binding of antigen to the B-cell antigen receptor (BCR) triggers signaling that ultimately leads to B-cell activation. (uniprot.org)
  • In B cells, Lyn sets the threshold of cell signaling and maintains the balance between activation and inhibition. (wikipedia.org)
  • Positive selection occurs through antigen-independent signaling involving both the pre-BCR and the BCR. (wikipedia.org)
  • genes
  • Transfer of alpha and beta TCR genes shows MHC-restricted antigen recognition by a single receptor. (wikipedia.org)
  • Also, since the levels of RORγ are rhythmic in some tissues (liver, kidney), it has been proposed to impose a circadian pattern of expression on a number of clock-controlled genes, for example the cell cycle regulator p21. (wikipedia.org)
  • downstream
  • As it has no known intrinsic enzymatic activity, the function of BLNK is to temporally and spatially coordinate and regulate signalling effectors downstream of the B cell receptor. (wikipedia.org)
  • gamma
  • We used mouse pre-B cell hybridoma subclones that had a human gamma (g) transgene (HUG1). (oxy.edu)
  • MIM 172420) and C-gamma-2 enzymes are controlled by receptor tyrosine kinases. (wikipedia.org)
  • T cell receptor gamma and delta rearrangements in hematologic malignancies. (wikipedia.org)
  • Key findings include determination of the first crystal structures of the following cytokine family members in complex with their surface receptors: gp130 family (IL-6), common gamma (γc) family (IL-2), Type I Interferons (IFNα2/IFNω) and Type III Interferons. (wikipedia.org)
  • engagement
  • Engagement of killer inhibitory receptors (KIR) disrupts the interaction of PLCG1 with LAT and blocks target cell-induced activation of PLC, maybe by inducing the dephosphorylation of LAT. (uniprot.org)
  • ligands
  • The same experimental system served the purpose to study the impact of TCR-ligation on developing T cells by MHC class I and MHC class II ligands on the intrathymic generation of CD8 killer and CD4 helper cells, respectively. (wikipedia.org)
  • regulation
  • CD27 cooperates with the pre-T cell receptor in the regulation of murine T cell development. (rupress.org)
  • The regulation of extracellular proteolytic activity via the plasminogen activation system is complex, involving numerous activators, inhibitors, and receptors. (biomedcentral.com)
  • Receptor-mediated cell-surface localisation of the various components of the PAS (for example, uPA, plg, and plg activator inhibitor type 1 [PAI-and type 2 [PAI- is critical for the spatial and temporal regulation of proteolysis. (biomedcentral.com)
  • In pancreatic islets, acts as a modulator of beta-cells function through the up-regulation of PDX1 and NKX6-1 and consequent stimulation of insulin secretion in response to glucose. (uniprot.org)
  • In various hematopoietic cells, Lyn has emerged as a key enzyme involved in the regulation of cell activation. (wikipedia.org)
  • CHMP5 is essential for late endosome function and down-regulation of receptor signalling during mouse embryogenesis. (wikipedia.org)
  • immune
  • Increased inflammation and activation of immune cells at the fetal-maternal interface in pre-eclampsia could influence the neonatal immune compartment. (wiley.com)
  • In a demonstration involving mast cells (a kind of cell in the immune system), Ingber and Mannix showed that the beads, when bound to cell receptors and exposed to a magnetic field, were able to stimulate an influx of calcium into the cells. (newswise.com)
  • MPS is part of the innate immune system and comprises of monocytes, macrophages, and dendritic cells (DC). (upenn.edu)
  • DCs and macrophages are thought to play important role in cancer by modulating host-immune responses against the tumor cells, promoting metastasis, angiogenesis, etc. (upenn.edu)
  • Dr. Ghosh has served in an advisory capacity for several organisations, including the Board of Scientific Counselors of the National Cancer Institute and the Advisory Board of the Center on Immune Receptors at the Karolinska Institute in Stockholm, Sweden. (wikipedia.org)
  • In Artemis-deficient individuals, V(D)J recombination is blocked because the hairpin ends cannot be opened, and so no mature B or T cells are produced, a condition known as severe combined immune deficiency (SCID). (wikipedia.org)
  • Presently Harald von Boehmer studies the generation and function of regulatory T cells that have an essential role in preventing autoimmunity with the goal to exploit these cells in the prevention of and interference with unwanted immune reactions. (wikipedia.org)
  • secretion
  • Calcium influx is a fundamental signal used by nerve cells to initiate nerve conduction, by heart and muscle cells to stimulate contractions and by other cells for secretion. (newswise.com)
  • activation
  • The existence of a proteolytic positive feedback loop in plasminogen activation has profound implications for the ability of breast cancer cells expressing high amounts of uPA to accumulate a large proteolytic capacity at the cell surface, thereby conferring invasive potential. (biomedcentral.com)
  • With FYN and LYN, plays an essential role in pre-B-cell receptor (pre-BCR)-mediated NF-kappa-B activation. (uniprot.org)
  • In turn, activation of the insulin receptor has been shown to increase autophosphorylation of Lyn suggesting a possible feedback loop. (wikipedia.org)
  • The function of BLNK was first illustrated in BLNK deficient DT40 cells, a chicken B-cell line, which exhibited an abrogated intracellular calcium mobilisation response and impaired activation of MAP kinases p38, JNK, and to a lesser degree ERK upon B-cell receptor (BCR) activation as compared to wild type DT40 cells. (wikipedia.org)
  • Activation of NF-{kappa}B promo tes the transition of large, CD43+ pre-B cells to small, CD43- pre-B cells. (wikipedia.org)
  • di Meglio, P., A. Ianaro, and S. Ghosh, Amelioration of acute inflammation by systemic administration of a cell-permeable peptide inhibitor of NF-kappaB activation. (wikipedia.org)
  • PDK1 nucleates T cell receptor-induced signalling complex for NF-kappaB activation. (wikipedia.org)
  • Garcia's research has established how structural and biophysical principles govern receptor binding and signal activation in many different cytokine systems. (wikipedia.org)
  • While immature and during the T1 phase, B cells express BCR of class IgH, but BCR expression changes to the classes IgM and IgD after transition into the T2 phase and while mature up to activation. (wikipedia.org)
  • B cell activation occurs in the secondary lymphoid organs (SLOs), such as the spleen and lymph nodes. (wikipedia.org)
  • Of the three B cell subsets, FO B cells preferentially undergo T cell-dependent activation while MZ B cells and B1 B cells preferentially undergo T cell-independent activation. (wikipedia.org)
  • tumors
  • Among lymphoid malignancies, we found an association between VpreB3 expression and B-cell tumors with c-MYC abnormalities. (haematologica.org)
  • development
  • The study presented here reveals that CD27 may play a similar role in thymic pre-T cell development. (rupress.org)
  • Therefore, we conclude that CD27 may contribute to normal murine T cell development by synergizing with the pre-TCR-mediated signal. (rupress.org)
  • It is expressed selectively at the early stages of B cell development, namely, in proB and early preB cells. (wikipedia.org)
  • Though no CD179a-related human disease or pathology has been reported yet, the deficiency of other components of preB cell receptor such as CD179b, Ig mu heavy chain and CD79a has been shown to result in severe impairment of B cell development and agammaglobulinemia in human. (wikipedia.org)
  • BTK is a kinase that plays a crucial role in B-cell development. (wikipedia.org)
  • In knockout mice, BLNK deficiency results in a partial block in B-cell development, and in humans BLNK deficiency results in a much more profound block in B-cell development. (wikipedia.org)
  • This is especially important in embryonic development as there are not enough resources to create a rich microvasculature with new cells every time a new vessel develops. (wikipedia.org)
  • B cells undergo two types of selection while developing in the bone marrow to ensure proper development. (wikipedia.org)
  • To complete development, immature B cells migrate from the bone marrow to the spleen as well as pass through two transitional stages: T1 and T2. (wikipedia.org)
  • molecules
  • Don Ingber, MD, PhD, and Robert Mannix, PhD, of Children's program in Vascular Biology, in collaboration with Mara Prentiss, PhD, a physicist at Harvard University, devised a way to get tiny beads " 30 nanometers (billionths of a meter) in diameter " to bind to receptor molecules on the cell surface. (newswise.com)
  • This pull drags the cell's receptors into large clusters, mimicking what happens when drugs or other molecules bind to them. (newswise.com)
  • As sprouts extend toward the source of the angiogenic stimulus, endothelial cells migrate in tandem, using adhesion molecules called integrins. (wikipedia.org)
  • expression
  • ELISAs and Western blots were used to verify expression and quantify amount of kappa produced in seven HUG + JH knockout cell lines. (oxy.edu)
  • Preeclampsia slightly influences CB monocyte receptor expression. (wiley.com)
  • While CB monocyte characteristics seemed unaffected, CB NK cells from pre-eclamptic pregnancies had higher NKp30, but borderline lower NKG2D expression. (wiley.com)
  • It also suggests the possibility that the potential for bivalent expression could represent a general feature of Ag receptors. (jimmunol.org)
  • Galectin-1 expression in Hodgkin Lymphoma has also been shown to mediate immunosuppression of CD8+ T-cells. (wikipedia.org)
  • surface
  • Monocytes and natural killer (NK) cells from cord blood (CB) of children with pre-eclamptic or healthy mothers were analyzed by flow cytometry for surface markers and intracellular cytokines. (wiley.com)
  • However, few studies have used techniques that exclusively characterise cell-surface events and these mechanisms have not been investigated at the breast cancer cell surface. (biomedcentral.com)
  • We have studied plasminogen binding to MCF-7 in which urokinase plasminogen activator receptor (uPAR) levels were upregulated by PMA (12- O -tetradecanoylphorbol-13-acetate) stimulation, allowing flexible and transient modulation of cell-surface uPA. (biomedcentral.com)
  • Cell-surface plasminogen binding was significantly enhanced in the presence of elevated levels of uPA in an activity-dependent manner and was greatly attenuated in the presence of the plasmin inhibitor aprotinin. (biomedcentral.com)
  • K. Christopher "Chris" Garcia, Ph.D., is an American scientist renowned for his research on the molecular biology of cell surface receptors. (wikipedia.org)
  • It can be found in the nucleus, the cytoplasm, the cell surface and in the extracellular space. (wikipedia.org)
  • In general, FGFs stimulate a variety of cellular functions by binding to cell surface FGF-receptors in the presence of heparin proteoglycans. (wikipedia.org)
  • lymphoid
  • In birds, B cells mature in the bursa of Fabricius, a lymphoid organ. (wikipedia.org)
  • HSCs first differentiate into multipotent progenitor (MPP) cells, then common lymphoid progenitor (CLP) cells. (wikipedia.org)
  • The tissue distribution of the second isoform, RORγt, appears to be highly restricted to the thymus where it is expressed exclusively in immature CD4+/CD8+ thymocytes and in lymphoid tissue inducer (LTi) cells. (wikipedia.org)
  • Immunity
  • In utero inflammatory priming of neonatal innate immunity taking place in pre-eclamptic pregnancies might influence specific NK cell functions in newborns. (wiley.com)
  • transmembrane
  • However, one major structural difference between these two receptors is that although transmembrane BCR and secreted Ab are at least bivalent, current models suggest that TCR is not. (jimmunol.org)
  • activator
  • Using techniques that preserve cell integrity, we characterise the role of uPA as both a plasminogen receptor and activator and quantify the relative contribution of pre-formed and cryptic plasminogen receptors to plasminogen binding. (biomedcentral.com)
  • regulate
  • Additionally, the ability of these cells to regulate lymphocyte function makes them an important determinant in the success of cancer immunotherapy. (upenn.edu)