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
















  • Retinoic acid is essential for Th1 cell lineage stability and prevents transition to a Th17 cell program.

    abstract::CD4(+) T cells differentiate into phenotypically distinct T helper cells upon antigenic stimulation. Regulation of plasticity between these CD4(+) T-cell lineages is critical for immune homeostasis and prevention of autoimmune disease. However, the factors that regulate lineage stability are largely unknown. Here we i...


    pub_type: 杂志文章


    authors: Brown CC,Esterhazy D,Sarde A,London M,Pullabhatla V,Osma-Garcia I,Al-Bader R,Ortiz C,Elgueta R,Arno M,de Rinaldis E,Mucida D,Lord GM,Noelle RJ

    更新日期:2015-03-17 00:00:00

  • Components of a Stat recognition code: evidence for two layers of molecular selectivity.

    abstract::Latent and activated forms of Stat1 and Stat6 have been expressed and purified, enabling biochemical experiments relating to their functional activities. Stat1 bound to a phosphotyrosine peptide derived from the IFN gamma receptor with a KD of 50 nM, whereas Stat6 bound to an IL-4 receptor peptide with a KD of 300 nM....


    pub_type: 杂志文章


    authors: Schindler U,Wu P,Rothe M,Brasseur M,McKnight SL

    更新日期:1995-06-01 00:00:00

  • Epstein-Barr virus coopts lipid rafts to block the signaling and antigen transport functions of the BCR.

    abstract::The B cell antigen receptor (BCR) functions to initiate signaling and to internalize antigen for processing from within Lyn kinase-enriched membrane lipid rafts. The signaling function of the BCR is blocked by Epstein-Barr Virus (EBV) latent membrane protein 2A (LMP2A), which is constitutively phosphorylated by Lyn. H...


    pub_type: 杂志文章


    authors: Dykstra ML,Longnecker R,Pierce SK

    更新日期:2001-01-01 00:00:00

  • Activation of the innate signaling molecule MAVS by bunyavirus infection upregulates the adaptor protein SARM1, leading to neuronal death.

    abstract::La Crosse virus (LACV), a zoonotic Bunyavirus, is a major cause of pediatric viral encephalitis in the United States. A hallmark of neurological diseases caused by LACV and other encephalitic viruses is the induction of neuronal cell death. Innate immune responses have been implicated in neuronal damage, but no mechan...


    pub_type: 杂志文章


    authors: Mukherjee P,Woods TA,Moore RA,Peterson KE

    更新日期:2013-04-18 00:00:00

  • Fli-1 is required for murine vascular and megakaryocytic development and is hemizygously deleted in patients with thrombocytopenia.

    abstract::The ETS gene Fli-1 is involved in the induction of erythroleukemia in mice by Friend murine leukemia virus and Ewings sarcoma in children. Mice with a targeted null mutation in the Fli-1 locus die at day 11.5 of embryogenesis with loss of vascular integrity leading to bleeding within the vascular plexus of the cerebra...


    pub_type: 杂志文章


    authors: Hart A,Melet F,Grossfeld P,Chien K,Jones C,Tunnacliffe A,Favier R,Bernstein A

    更新日期:2000-08-01 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

  • GADD45gamma mediates the activation of the p38 and JNK MAP kinase pathways and cytokine production in effector TH1 cells.

    abstract::The p38 and JNK stress-activated MAPK signal transduction pathways are activated by T cell receptor (TCR) signaling and are required for IFN-gamma production by TH1 effector cells. Here, we show that the expression of GADD45gamma is induced during T cell activation and that the level of expression is higher in TH1 cel...


    pub_type: 杂志文章


    authors: Lu B,Yu H,Chow C,Li B,Zheng W,Davis RJ,Flavell RA

    更新日期:2001-05-01 00:00:00

  • TRAF2 differentially regulates the canonical and noncanonical pathways of NF-kappaB activation in mature B cells.

    abstract::To examine the role of the TNF-R superfamily signaling protein TRAF2 in mature B cell development and NF-kappaB activation, conditionally TRAF2-deficient mice were produced. B cells lacking TRAF2 expression in these mice possessed a selective survival advantage, accumulated in the lymph nodes and splenic marginal zone...


    pub_type: 杂志文章


    authors: Grech AP,Amesbury M,Chan T,Gardam S,Basten A,Brink R

    更新日期:2004-11-01 00:00:00

  • alpha beta T cell development is abolished in mice lacking both Lck and Fyn protein tyrosine kinases.

    abstract::Two families of protein tyrosine kinases (PTKs), the Src and Syk/ZAP-70 families, are required for T cell development. Lck is the major Src family member required for thymopoiesis, since there is a severe deficit of CD4+CD8+ thymocytes and mature T cells in its absence. However, some peripheral T cells are evident in ...


    pub_type: 杂志文章


    authors: van Oers NS,Lowin-Kropf B,Finlay D,Connolly K,Weiss A

    更新日期:1996-11-01 00:00:00

  • The quest for CD8+ memory stem cells.

    abstract::In this issue of Immunity, Turtle et al. (2009) describe the identification of a distinct CD8(+) memory T cell subset in humans, which could bring us closer to the identification of the enigmatic "memory stem cell." ...


    pub_type: 评论,杂志文章


    authors: Neuenhahn M,Busch DH

    更新日期:2009-11-20 00:00:00

  • Lysosomal trafficking, antigen presentation, and microbial killing are controlled by the Arf-like GTPase Arl8b.

    abstract::Antigen presentation and microbial killing are critical arms of host defense that depend upon cargo trafficking into lysosomes. Yet, the molecular regulators of traffic into lysosomes are only partly understood. Here, using a lysosome-dependent immunological screen of a trafficking shRNA library, we identified the Arf...


    pub_type: 杂志文章


    authors: Garg S,Sharma M,Ung C,Tuli A,Barral DC,Hava DL,Veerapen N,Besra GS,Hacohen N,Brenner MB

    更新日期:2011-08-26 00:00:00

  • Inflammatory monocytes recruited to allergic skin acquire an anti-inflammatory M2 phenotype via basophil-derived interleukin-4.

    abstract::Monocytes and macrophages are important effectors and regulators of inflammation, and both can be divided into distinct subsets based on their phenotypes. The developmental and functional relationship between individual subsets of monocytes and those of macrophages has not been fully elucidated, although Ly6C(+)CCR2(+...


    pub_type: 杂志文章


    authors: Egawa M,Mukai K,Yoshikawa S,Iki M,Mukaida N,Kawano Y,Minegishi Y,Karasuyama H

    更新日期:2013-03-21 00:00:00

  • Nonpathogenic SIV infection of sooty mangabeys is characterized by limited bystander immunopathology despite chronic high-level viremia.

    abstract::HIV-infected humans and SIV-infected rhesus macaques who remain healthy despite long-term infection exhibit exceptionally low levels of virus replication and active antiviral cellular immune responses. In contrast, sooty mangabey monkeys that represent natural hosts for SIV infection do not develop AIDS despite high l...


    pub_type: 杂志文章


    authors: Silvestri G,Sodora DL,Koup RA,Paiardini M,O'Neil SP,McClure HM,Staprans SI,Feinberg MB

    更新日期:2003-03-01 00:00:00

  • Functional characterization of a novel hematopoietic stem cell and its place in the c-Kit maturation pathway in bone marrow cell development.

    abstract::While the majority of purified pluripotential hematopoietic stem cells (PHSC) express c-Kit, the receptor for steel factor, we have phenotypically and functionally separated a distinct class of PHSC that does not express c-Kit. In contrast to c-Kit-positive (c-Kit(pos)) PHSC, the c-Kit-negative (c-Kit(neg)) PHSC do no...


    pub_type: 杂志文章


    authors: Ortiz M,Wine JW,Lohrey N,Ruscetti FW,Spence SE,Keller JR

    更新日期:1999-02-01 00:00:00

  • Functional specializations of human epidermal Langerhans cells and CD14+ dermal dendritic cells.

    abstract::Little is known about the functional differences between the human skin myeloid dendritic cell (DC) subsets, epidermal CD207(+) Langerhans cells (LCs) and dermal CD14(+) DCs. We showed that CD14(+) DCs primed CD4(+) T cells into cells that induce naive B cells to switch isotype and become plasma cells. In contrast, LC...


    pub_type: 杂志文章


    authors: Klechevsky E,Morita R,Liu M,Cao Y,Coquery S,Thompson-Snipes L,Briere F,Chaussabel D,Zurawski G,Palucka AK,Reiter Y,Banchereau J,Ueno H

    更新日期:2008-09-19 00:00:00

  • The E3 ubiquitin ligase Pellino3 protects against obesity-induced inflammation and insulin resistance.

    abstract::Diet-induced obesity can induce low-level inflammation and insulin resistance. Interleukin-1β (IL-1β) is one of the key proinflammatory cytokines that contributes to the generation of insulin resistance and diabetes, but the mechanisms that regulate obesity-driven inflammation are ill defined. Here we found reduced ex...


    pub_type: 杂志文章


    authors: Yang S,Wang B,Humphries F,Hogan AE,O'Shea D,Moynagh PN

    更新日期:2014-12-18 00:00:00

  • Memory B cells from human tonsils colonize mucosal epithelium and directly present antigen to T cells by rapid up-regulation of B7-1 and B7-2.

    abstract::Human memory B cells that carry mutated IgV region genes were isolated from tonsils by negative selection of IgD+ naive B cells and CD38+ germinal center B cells and plasma cells. They were mainly found within the intraepithelial areas, but not in the B cell follicles of human tonsils. Memory B cells but not naive B c...


    pub_type: 杂志文章


    authors: Liu YJ,Barthélémy C,de Bouteiller O,Arpin C,Durand I,Banchereau J

    更新日期:1995-03-01 00:00:00

  • The small GTPase Rac2 controls phagosomal alkalinization and antigen crosspresentation selectively in CD8(+) dendritic cells.

    abstract::A unique subpopulation of spleen dendritic cells (DCs) that express the CD8 surface marker efficiently present phagocytosed antigens to CD8(+) T lymphocytes in a process called "crosspresentation," which initiates cytotoxic immune responses. We now show that the small GTPase Rac2 plays a critical role in antigen cross...


    pub_type: 杂志文章


    authors: Savina A,Peres A,Cebrian I,Carmo N,Moita C,Hacohen N,Moita LF,Amigorena S

    更新日期:2009-04-17 00:00:00

  • Human tyk2 kinase deficiency: another primary immunodeficiency syndrome.

    abstract::Janus kinases are critical for cytokine signaling. Mutations of Jak3 cause primary immunodeficiency, but Minegishi et al. (2006) now show that mutation of another Jak, tyrosine kinase 2, underlies another human immunodeficiency syndrome. ...


    pub_type: 杂志文章,评审


    authors: Watford WT,O'Shea JJ

    更新日期:2006-11-01 00:00:00

  • Notch receptors and Smad3 signaling cooperate in the induction of interleukin-9-producing T cells.

    abstract::Interleukin 9 (IL-9) is a pleiotropic cytokine that can regulate autoimmune responses by enhancing regulatory CD4(+)FoxP3(+) T regulatory (Treg) cell survival and T helper 17 (Th17) cell proliferation. Here, we analyzed the costimulatory requirements for the induction of Th9 cells, and demonstrated that Notch pathway ...


    pub_type: 杂志文章


    authors: Elyaman W,Bassil R,Bradshaw EM,Orent W,Lahoud Y,Zhu B,Radtke F,Yagita H,Khoury SJ

    更新日期:2012-04-20 00:00:00

  • Superficial Immunity: Antimicrobial Responses Are More Than Skin Deep.

    abstract::The skin barrier is essential for host defense, but how the skin provides protection when the barrier is breached is not well understood. In this issue of Immunity, Gallo and colleagues report that keratinocytes integrate signals from antimicrobial peptides via MAVS signaling to amplify their antiviral immune response...


    pub_type: 评论,杂志文章


    authors: Mack MR,Kim BS

    更新日期:2016-07-19 00:00:00

  • Caspases in Cell Death, Inflammation, and Disease.

    abstract::Caspases are an evolutionary conserved family of cysteine proteases that are centrally involved in cell death and inflammation responses. A wealth of foundational insight into the molecular mechanisms that control caspase activation has emerged in recent years. Important advancements include the identification of addi...


    pub_type: 杂志文章,评审


    authors: Van Opdenbosch N,Lamkanfi M

    更新日期:2019-06-18 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

  • The distal V(H) gene cluster of the Igh locus contains distinct regulatory elements with Pax5 transcription factor-dependent activity in pro-B cells.

    abstract::V(H)-DJ(H) recombination of the immunoglobulin heavy chain (Igh) locus is temporally and spatially controlled during early B cell development, and yet no regulatory elements other than the V(H) gene promoters have been identified throughout the entire V(H) gene cluster. Here, we discovered regulatory sequences that ar...


    pub_type: 杂志文章


    authors: Ebert A,McManus S,Tagoh H,Medvedovic J,Salvagiotto G,Novatchkova M,Tamir I,Sommer A,Jaritz M,Busslinger M

    更新日期:2011-02-25 00:00:00

  • Priming the pump: adhesion enhances T cell antigen receptor-induced signaling.

    abstract::In this issue of Immunity, Conche et al. (2009) define an antigen-independent signaling pathway that is dependent on cyclic adenosine monophosphate and extracellular signal-regulated kinase and T cells for subsequent T cell antigen receptor signaling. ...


    pub_type: 评论,杂志文章


    authors: Kortum RL,Samelson LE

    更新日期:2009-01-16 00:00:00

  • A role for the endoplasmic reticulum protein retrotranslocation machinery during crosspresentation by dendritic cells.

    abstract::Crosspresentation of exogenous antigens (Ags) to CD8(+) T cells by dendritic cells generally requires their entry into the cytosol. Here we show that both soluble and phagocytosed extracellular Ags accessed the cytosol via molecular components required for endoplasmic reticulum (ER)-associated degradation (ERAD). Exog...


    pub_type: 杂志文章


    authors: Ackerman AL,Giodini A,Cresswell P

    更新日期:2006-10-01 00:00:00

  • Notch 1 signaling regulates peripheral T cell activation.

    abstract::Notch signaling has been identified as an important regulator of leukocyte differentiation and thymic maturation. Less is known about the role of Notch signaling in regulating mature T cells. We examined the role of Notch 1 in regulating peripheral T cell activity in vitro and in vivo. Coligation of Notch 1 together w...


    pub_type: 杂志文章


    authors: Eagar TN,Tang Q,Wolfe M,He Y,Pear WS,Bluestone JA

    更新日期:2004-04-01 00:00:00

  • Oxidative damage of DNA confers resistance to cytosolic nuclease TREX1 degradation and potentiates STING-dependent immune sensing.

    abstract::Immune sensing of DNA is critical for antiviral immunity but can also trigger autoimmune diseases such as lupus erythematosus (LE). Here we have provided evidence for the involvement of a damage-associated DNA modification in the detection of cytosolic DNA. The oxidized base 8-hydroxyguanosine (8-OHG), a marker of oxi...


    pub_type: 杂志文章


    authors: Gehrke N,Mertens C,Zillinger T,Wenzel J,Bald T,Zahn S,Tüting T,Hartmann G,Barchet W

    更新日期:2013-09-19 00:00:00

  • Rulers over randomness: stroma cells guide lymphocyte migration in lymph nodes.

    abstract::How is the amoeboid movement of lymphocytes in secondary lymphoid organs orchestrated? In this issue of Immunity, Bajénoff et al. (2006) demonstrate that stromal cell networks serve as guidance structures that direct and limit the migration of B and T cells in lymph nodes. ...


    pub_type: 评论,杂志文章,评审


    authors: Mempel TR,Junt T,von Andrian UH

    更新日期:2006-12-01 00:00:00

  • Systemic effects of inflammation on health during chronic HIV infection.

    abstract::Combination antiretroviral therapy for HIV infection improves immune function and eliminates the risk of AIDS-related complications but does not restore full health. HIV-infected adults have excess risk of cardiovascular, liver, kidney, bone, and neurologic diseases. Many markers of inflammation are elevated in HIV di...


    pub_type: 杂志文章


    authors: Deeks SG,Tracy R,Douek DC

    更新日期:2013-10-17 00:00:00