Essential role for cathepsin S in MHC class II-associated invariant chain processing and peptide loading.


:Destruction of li by proteolysis is required for MHC class II molecules to bind antigenic peptides, and for transport of the resulting complexes to the cell surface. The cysteine protease cathepsin S is highly expressed in spleen, lymphocytes, monocytes, and other class II-positive cells, and is inducible with interferon-gamma. Specific inhibition of cathepsin S in B lymphoblastoid cells prevented complete proteolysis of li, resulting in accumulation of a class II-associated 13 kDa li fragment in vivo. Consequently, the formation of SDS-stable complexes was markedly reduced. Purified cathepsin S, but not cathepsin B, H, or D, specifically digested li from alpha beta li trimers, generating alpha beta-CLIP complexes capable of binding exogenously added peptide in vitro. Thus, cathepsin S is essential in B cells for effective li proteolysis necessary to render class II molecules competent for binding peptides.






Riese RJ,Wolf PR,Brömme D,Natkin LR,Villadangos JA,Ploegh HL,Chapman HA




Has Abstract


1996-04-01 00:00:00
















  • The Immune Landscape of Cancer.

    abstract::We performed an extensive immunogenomic analysis of more than 10,000 tumors comprising 33 diverse cancer types by utilizing data compiled by TCGA. Across cancer types, we identified six immune subtypes-wound healing, IFN-γ dominant, inflammatory, lymphocyte depleted, immunologically quiet, and TGF-β dominant-character...


    pub_type: 杂志文章


    authors: Thorsson V,Gibbs DL,Brown SD,Wolf D,Bortone DS,Ou Yang TH,Porta-Pardo E,Gao GF,Plaisier CL,Eddy JA,Ziv E,Culhane AC,Paull EO,Sivakumar IKA,Gentles AJ,Malhotra R,Farshidfar F,Colaprico A,Parker JS,Mose LE,Vo NS,L

    更新日期:2018-04-17 00:00:00

  • Stroma-derived interleukin-34 controls the development and maintenance of langerhans cells and the maintenance of microglia.

    abstract::Colony stimulating factor-1 (Csf-1) receptor and its ligand Csf-1 control macrophage development, maintenance, and function. The development of both Langerhans cells (LCs) and microglia is highly dependent on Csf-1 receptor signaling but independent of Csf-1. Here we show that in both mice and humans, interleukin-34 (...


    pub_type: 杂志文章


    authors: Greter M,Lelios I,Pelczar P,Hoeffel G,Price J,Leboeuf M,Kündig TM,Frei K,Ginhoux F,Merad M,Becher B

    更新日期:2012-12-14 00:00:00

  • Monomeric and oligomeric complexes of the B cell antigen receptor.

    abstract::The current structural model of the B cell antigen receptor (BCR) describes it as a symmetric protein complex in which one membrane-bound immunoglobulin molecule (mIg) is noncovalently bound on each side by an Ig-alpha/Ig-beta heterodimer. Using peptide-tagged Ig-alpha proteins, blue native polyacrylamide gel electrop...


    pub_type: 杂志文章


    authors: Schamel WW,Reth M

    更新日期:2000-07-01 00:00:00

  • Molecular and Functional Characterization of Lymphoid Progenitor Subsets Reveals a Bipartite Architecture of Human Lymphopoiesis.

    abstract::The classical model of hematopoiesis established in the mouse postulates that lymphoid cells originate from a founder population of common lymphoid progenitors. Here, using a modeling approach in humanized mice, we showed that human lymphoid development stemmed from distinct populations of CD127- and CD127+ early lymp...


    pub_type: 杂志文章


    authors: Alhaj Hussen K,Vu Manh TP,Guimiot F,Nelson E,Chabaane E,Delord M,Barbier M,Berthault C,Dulphy N,Alberdi AJ,Burlen-Defranoux O,Socié G,Bories JC,Larghero J,Vanneaux V,Verhoeyen E,Wirth T,Dalod M,Gluckman JC,Cumano A

    更新日期:2017-10-17 00:00:00

  • Increased CD95/Fas-induced apoptosis of HIV-specific CD8(+) T cells.

    abstract::Why HIV-specific CD8(+) T cells ultimately fail to clear or control HIV infection is not known. We show here that HIV-specific CD8(+) T cells exhibit increased sensitivity to CD95/Fas-induced apoptosis. This apoptosis is 3-fold higher compared to CMV-specific CD8(+) T cells from the same patients. HIV-specific CD8(+) ...


    pub_type: 杂志文章


    authors: Mueller YM,De Rosa SC,Hutton JA,Witek J,Roederer M,Altman JD,Katsikis PD

    更新日期:2001-12-01 00:00:00

  • Antisocial networking in T helper cells.

    abstract::T helper cell differentiation is controlled by a network of transcription factors. In this issue of Immunity, Yagi et al. (2010) describe the opposing effects of transcription factors Runx3 and GATA3 in the network promoting T helper 1 cell development. ...


    pub_type: 评论,杂志文章


    authors: Pham D,Kaplan MH

    更新日期:2010-04-23 00:00:00

  • Cell Survival and Cytokine Release after Inflammasome Activation Is Regulated by the Toll-IL-1R Protein SARM.

    abstract::Assembly of inflammasomes after infection or injury leads to the release of interleukin-1β (IL-1β) and to pyroptosis. After inflammasome activation, cells either pyroptose or enter a hyperactivated state defined by IL-1β secretion without cell death, but what controls these different outcomes is unknown. Here, we show...


    pub_type: 杂志文章


    authors: Carty M,Kearney J,Shanahan KA,Hams E,Sugisawa R,Connolly D,Doran CG,Muñoz-Wolf N,Gürtler C,Fitzgerald KA,Lavelle EC,Fallon PG,Bowie AG

    更新日期:2019-06-18 00:00:00

  • Stat5 activation plays a critical role in Th2 differentiation.

    abstract::Upon TCR engagement, naive CD4 T cells differentiate toward the Th1 or Th2 phenotype. IL-4, acting through Stat6, plays a major role in Th2 differentiation; IL-2 has also been reported to be essential. Here, we report that retroviral (RV)-mediated expression of a constitutively active Stat5A mutant (STAT5A1*6) can ful...


    pub_type: 杂志文章


    authors: Zhu J,Cote-Sierra J,Guo L,Paul WE

    更新日期:2003-11-01 00:00:00

  • WECHE: a novel hematopoietic regulatory factor.

    abstract::Previously, we described AGM-derived endothelial cell lines that either inhibited or permitted the development of erythroid or B cells. We utilized a differential gene expression method to isolate a chemokine, termed WECHE, from one of these cell lines. WECHE inhibited the formation of erythroid cells but had no effec...


    pub_type: 杂志文章


    authors: Ohneda O,Ohneda K,Nomiyama H,Zheng Z,Gold SA,Arai F,Miyamoto T,Taillon BE,McIndoe RA,Shimkets RA,Lewin DA,Suda T,Lasky LA

    更新日期:2000-02-01 00:00:00

  • Inhibition of IFN-gamma signaling by an Epstein-Barr virus immediate-early protein.

    abstract::Viruses have evolved elaborate mechanisms to target many aspects of the host's immune response. The cytokine IFN-gamma plays a central role in resistance of the host to infection via direct antiviral effects as well as modulation of the immune response. In this study, we demonstrate that the Epstein-Barr virus (EBV) i...


    pub_type: 杂志文章


    authors: Morrison TE,Mauser A,Wong A,Ting JP,Kenney SC

    更新日期:2001-11-01 00:00:00

  • Peptide antigen treatment of naive and virus-immune mice: antigen-specific tolerance versus immunopathology.

    abstract::Peptide-specific down-regulation of T cell responses may represent a powerful tool to intervene in autoimmune diseases or graft rejections. It is therefore important to know whether peptide treatment tolerizes both naive and antigen-experienced memory T lymphocytes. Here we show that a major histocompatibility complex...


    pub_type: 杂志文章


    authors: Aichele P,Brduscha-Riem K,Oehen S,Odermatt B,Zinkernagel RM,Hengartner H,Pircher H

    更新日期:1997-05-01 00:00:00

  • Regulatory T cells sequentially migrate from inflamed tissues to draining lymph nodes to suppress the alloimmune response.

    abstract::To determine the site and mechanism of suppression by regulatory T (Treg) cells, we investigated their migration and function in an islet allograft model. Treg cells first migrated from blood to the inflamed allograft where they were essential for the suppression of alloimmunity. This process was dependent on the chem...


    pub_type: 杂志文章


    authors: Zhang N,Schröppel B,Lal G,Jakubzick C,Mao X,Chen D,Yin N,Jessberger R,Ochando JC,Ding Y,Bromberg JS

    更新日期:2009-03-20 00:00:00

  • Interleukin-23 drives intestinal inflammation through direct activity on T cells.

    abstract::Mutations in the IL23R gene are linked to inflammatory bowel disease susceptibility. Experimental models have shown that interleukin-23 (IL-23) orchestrates innate and T cell-dependent colitis; however, the cell populations it acts on to induce intestinal immune pathology are unknown. Here, using Il23r(-/-) T cells, w...


    pub_type: 杂志文章


    authors: Ahern PP,Schiering C,Buonocore S,McGeachy MJ,Cua DJ,Maloy KJ,Powrie F

    更新日期:2010-08-27 00:00:00

  • Nucleic Acid Sensors as Therapeutic Targets for Human Disease.

    abstract::Innate immune sensors that detect nucleic acids are attractive targets for therapeutic intervention because of their diverse roles in many disease processes. In detecting RNA and DNA from either self or non-self, nucleic acid sensors mediate the pathogenesis of many autoimmune and inflammatory conditions. Despite prom...


    pub_type: 杂志文章,评审


    authors: McWhirter SM,Jefferies CA

    更新日期:2020-07-14 00:00:00

  • Rank signaling links the development of invariant γδ T cell progenitors and Aire(+) medullary epithelium.

    abstract::The thymic medulla provides a specialized microenvironment for the negative selection of T cells, with the presence of autoimmune regulator (Aire)-expressing medullary thymic epithelial cells (mTECs) during the embryonic-neonatal period being both necessary and sufficient to establish long-lasting tolerance. Here we s...


    pub_type: 杂志文章


    authors: Roberts NA,White AJ,Jenkinson WE,Turchinovich G,Nakamura K,Withers DR,McConnell FM,Desanti GE,Benezech C,Parnell SM,Cunningham AF,Paolino M,Penninger JM,Simon AK,Nitta T,Ohigashi I,Takahama Y,Caamano JH,Hayday AC,La

    更新日期:2012-03-23 00:00:00

  • PGRP-SD, an Extracellular Pattern-Recognition Receptor, Enhances Peptidoglycan-Mediated Activation of the Drosophila Imd Pathway.

    abstract::Activation of the innate immune response in Metazoans is initiated through the recognition of microbes by host pattern-recognition receptors. In Drosophila, diaminopimelic acid (DAP)-containing peptidoglycan from Gram-negative bacteria is detected by the transmembrane receptor PGRP-LC and by the intracellular receptor...


    pub_type: 杂志文章


    authors: Iatsenko I,Kondo S,Mengin-Lecreulx D,Lemaitre B

    更新日期:2016-11-15 00:00:00

  • Infected cells call their killers to the scene of the crime.

    abstract::Effector CD8(+) T cells scan tissues to locate and kill infected host cells. In this issue of Immunity, Hickman et al. (2015) show that the exploration is not random: infected monocytes attract their assassins by secreting chemokines, which accelerates clearance of epicutaneous vaccinia virus infection. ...


    pub_type: 评论,杂志文章


    authors: Beura LK,Masopust D

    更新日期:2015-03-17 00:00:00

  • Dichotomous Expression of TNF Superfamily Ligands on Antigen-Presenting Cells Controls Post-priming Anti-viral CD4+ T Cell Immunity.

    abstract::T cell antigen-presenting cell (APC) interactions early during chronic viral infection are crucial for determining viral set point and disease outcome, but how and when different APC subtypes contribute to these outcomes is unclear. The TNF receptor superfamily (TNFRSF) member GITR is important for CD4+ T cell accumul...


    pub_type: 杂志文章


    authors: Chang YH,Wang KC,Chu KL,Clouthier DL,Tran AT,Torres Perez MS,Zhou AC,Abdul-Sater AA,Watts TH

    更新日期:2017-11-21 00:00:00

  • Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches.

    abstract::In the bone marrow, the special microenvironment niches nurture a pool of hematopoietic stem cells (HSCs). Many HSCs reside near the vasculature, but the molecular regulatory mechanism of niches for HSC maintenance remains unclear. Here we showed that the induced deletion of CXCR4, a receptor for CXC chemokine ligand ...


    pub_type: 杂志文章


    authors: Sugiyama T,Kohara H,Noda M,Nagasawa T

    更新日期:2006-12-01 00:00:00

  • Regulation of T helper 17 differentiation by orphan nuclear receptors: it's not just ROR gamma t anymore.

    abstract::T cells that produce IL-17 (T helper 17 cells) are implicated in autoimmune pathogenesis. In this issue of Immunity, Yang et al. (2008) report that the closely related orphan nuclear receptors ROR alpha and ROR gamma t work together to regulate T helper (Th)17 cell differentiation. ...


    pub_type: 评论,杂志文章


    authors: Sundrud MS,Rao A

    更新日期:2008-01-01 00:00:00

  • Down-regulation of IL-4 gene transcription and control of Th2 cell differentiation by a mechanism involving NFAT1.

    abstract::Transcription factors of the NFAT family play a critical role in the immune response by activating the expression of cytokines and other inducible genes in antigen-stimulated cells. Here we show that a member of this family, NFAT1, is involved in down-regulating the late phase of IL-4 gene transcription, thus inhibiti...


    pub_type: 杂志文章


    authors: Kiani A,Viola JP,Lichtman AH,Rao A

    更新日期:1997-12-01 00:00:00

  • Bile Acids Control Inflammation and Metabolic Disorder through Inhibition of NLRP3 Inflammasome.

    abstract::Reciprocal interactions between the metabolic system and immune cells play pivotal roles in diverse inflammatory diseases, but the underlying mechanisms remain elusive. The activation of bile acid-mediated signaling has been linked to improvement in metabolic syndromes and enhanced control of inflammation. Here, we de...


    pub_type: 杂志文章


    authors: Guo C,Xie S,Chi Z,Zhang J,Liu Y,Zhang L,Zheng M,Zhang X,Xia D,Ke Y,Lu L,Wang D

    更新日期:2016-10-18 00:00:00

  • Deficient T cell fate specification in mice with an induced inactivation of Notch1.

    abstract::Notch proteins are cell surface receptors that mediate developmental cell specification events. To explore the function of murine Notch1, an essential portion of the gene was flanked with loxP sites and inactivation induced via interferon-regulated Cre recombinase. Mice with a neonatally induced loss of Notch1 functio...


    pub_type: 杂志文章


    authors: Radtke F,Wilson A,Stark G,Bauer M,van Meerwijk J,MacDonald HR,Aguet M

    更新日期:1999-05-01 00:00:00

  • The chemokine receptor CXCR6 controls the functional topography of interleukin-22 producing intestinal innate lymphoid cells.

    abstract::Interleukin-22 (IL-22) plays a critical role in mucosal defense, although the molecular mechanisms that ensure IL-22 tissue distribution remain poorly understood. We show that the CXCL16-CXCR6 chemokine-chemokine receptor axis regulated group 3 innate lymphoid cell (ILC3) diversity and function. CXCL16 was constitutiv...


    pub_type: 杂志文章


    authors: Satoh-Takayama N,Serafini N,Verrier T,Rekiki A,Renauld JC,Frankel G,Di Santo JP

    更新日期:2014-11-20 00:00:00

  • Beta1 integrin is not essential for hematopoiesis but is necessary for the T cell-dependent IgM antibody response.

    abstract::Several experimental evidences suggested that beta1 integrin-mediated adhesion of hematopoietic stem cells (HSC) is important for their function in the bone marrow (BM). Using induced deletion of the beta1 integrin gene restricted to the hematopoietic system, we show that beta1 integrin is not essential for HSC retent...


    pub_type: 杂志文章


    authors: Brakebusch C,Fillatreau S,Potocnik AJ,Bungartz G,Wilhelm P,Svensson M,Kearney P,Körner H,Gray D,Fässler R

    更新日期:2002-03-01 00:00:00

  • Dynamic actin polymerization drives T cell receptor-induced spreading: a role for the signal transduction adaptor LAT.

    abstract::T cell activation induces functional changes in cell shape and cytoskeletal architecture. To facilitate the collection of dynamic, high-resolution images of activated T cells, we plated T cells on coverslips coated with antibodies to the T cell receptor (TCR). Using these images, we were able to quantitate the morphol...


    pub_type: 杂志文章


    authors: Bunnell SC,Kapoor V,Trible RP,Zhang W,Samelson LE

    更新日期:2001-03-01 00:00:00

  • Follicular Dendritic Cell Activation by TLR Ligands Promotes Autoreactive B Cell Responses.

    abstract::A hallmark of autoimmunity in murine models of lupus is the formation of germinal centers (GCs) in lymphoid tissues where self-reactive B cells expand and differentiate. In the host response to foreign antigens, follicular dendritic cells (FDCs) maintain GCs through the uptake and cycling of complement-opsonized immun...


    pub_type: 杂志文章


    authors: Das A,Heesters BA,Bialas A,O'Flynn J,Rifkin IR,Ochando J,Mittereder N,Carlesso G,Herbst R,Carroll MC

    更新日期:2017-01-17 00:00:00

  • Bruton's tyrosine kinase and phospholipase Cgamma2 mediate chemokine-controlled B cell migration and homing.

    abstract::Control of integrin-mediated adhesion and migration by chemokines plays a critical role in B cell development, differentiation, and function; however, the underlying signaling mechanisms are poorly defined. Here we show that the chemokine SDF-1 induced activation of Bruton's tyrosine kinase (Btk) and that integrin-med...


    pub_type: 杂志文章


    authors: de Gorter DJ,Beuling EA,Kersseboom R,Middendorp S,van Gils JM,Hendriks RW,Pals ST,Spaargaren M

    更新日期:2007-01-01 00:00:00

  • Epigenetic instability of cytokine and transcription factor gene loci underlies plasticity of the T helper 17 cell lineage.

    abstract::Phenotypic plasticity of T helper 17 (Th17) cells suggests instability of chromatin structure of key genes of this lineage. We identified epigenetic modifications across the clustered Il17a and Il17f and the Ifng loci before and after differential IL-12 or TGF-beta cytokine signaling, which induce divergent fates of T...


    pub_type: 杂志文章


    authors: Mukasa R,Balasubramani A,Lee YK,Whitley SK,Weaver BT,Shibata Y,Crawford GE,Hatton RD,Weaver CT

    更新日期:2010-05-28 00:00:00

  • Histone Deacetylase SIRT1 Negatively Regulates the Differentiation of Interleukin-9-Producing CD4(+) T Cells.

    abstract::Distinct metabolic programs support the differentiation of CD4(+) T cells into separate functional subsets. In this study, we investigated metabolic mechanisms underlying the differentiation of IL-9-producing CD4(+) T cells (Th9) in allergic airway inflammation and cancerous tumors. We found that histone deacetylase S...


    pub_type: 杂志文章


    authors: Wang Y,Bi Y,Chen X,Li C,Li Y,Zhang Z,Wang J,Lu Y,Yu Q,Su H,Yang H,Liu G

    更新日期:2016-06-21 00:00:00