Abstract:
:The complement system plays a central role in a number of human inflammatory diseases, and there is a significant need for development of complement-directed therapies. The discovery of an arsenal of anti-complement proteins secreted by the pathogen Staphylococcus aureus brought with it the potential for harnessing the powerful inhibitory properties of these molecules. One such family of inhibitors, the SCINs, interact with a functional "hot-spot" on the surface of C3b. SCINs not only stabilize an inactive form of the alternative pathway (AP) C3 convertase (C3bBb), but also overlap the C3b binding site of complement factors B and H. Here we determined that a conserved Arg residue in SCINs is critical for function of full-length SCIN proteins. Despite this, we also found SCIN-specific differences in the contributions of other residues found at the C3b contact site, which suggested that a more diverse repertoire of residues might be able to recognize this region of C3b. To investigate this possibility, we conducted a phage display screen aimed at identifying SCIN-competitive 12-mer peptides. In total, seven unique sequences were identified and all exhibited direct C3b binding. A subset of these specifically inhibited the AP in assays of complement function. The mechanism of AP inhibition by these peptides was probed through surface plasmon resonance approaches, which revealed that six of the seven peptides disrupted C3bBb formation by interfering with factor B/C3b binding. To our knowledge this study has identified the first small molecules that retain inhibitory properties of larger staphylococcal immune evasion proteins.
journal_name
Mol Immunoljournal_title
Molecular immunologyauthors
Summers BJ,Garcia BL,Woehl JL,Ramyar KX,Yao X,Geisbrecht BVdoi
10.1016/j.molimm.2015.05.012subject
Has Abstractpub_date
2015-10-01 00:00:00pages
193-205issue
2 Pt Beissn
0161-5890issn
1872-9142pii
S0161-5890(15)00405-8journal_volume
67pub_type
杂志文章abstract::Excessive production of pro-inflammatory cytokines such as interleukin-1β (IL-1β) plays a key role in the pathophysiological development of osteoarthritis (OA). Orexin A is an important peptide of hypothalamic origin, which has displayed its multiple biological functions in several chronic diseases via activation of i...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2018.05.012
更新日期:2018-09-01 00:00:00
abstract::T cell responses are determined by the environment in which antigen is encountered. In the absence of proper costimulation, anergizing stimuli induce the activation of a specific program of gene expression. Proteins encoded by these genes impose a state of functional unresponsiveness in anergic T cells through the act...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2008.09.029
更新日期:2009-02-01 00:00:00
abstract::Polyclonal or monoclonal human IgM rheumatoid factors (RF) react with eight antigenic sites on the CH3 IgG domain, four sites on CH2 and two on human beta 2-microglobulin. All 14 of these RF-reactive epitopes are linear 7-11 amino acid peptides with different primary sequence. We questioned whether RF reactivity with ...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/s0161-5890(97)00024-2
更新日期:1997-05-01 00:00:00
abstract::The recognition structure responsible for binding to conventional antigen on target cells has not previously been described for nonspecific cytotoxic cells (NCC) or for mammalian natural killer (NK) cells. Although several biochemical pathways may be available for initiation of the lytic cycle in NCC, evidence present...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/s0161-5890(97)00086-2
更新日期:1997-08-01 00:00:00
abstract::The complement (C) inflammatory cascade is part of the phylogenetically ancient innate immune response and is crucial to our natural ability to ward off infection. It has three critical physiologic activities: (i) defending against microbial infections by triggering the generation of a membranolytic complex (C5b9 comp...
journal_title:Molecular immunology
pub_type: 杂志文章,评审
doi:10.1016/j.molimm.2004.06.011
更新日期:2004-11-01 00:00:00
abstract::Several mutations in the CFH gene have been described in non-Shiga-toxin-associated haemolytic uraemic syndrome (non-Stx-HUS), a rare syndrome characterized by haemolytic anaemia, thrombocytopenia and acute renal failure. Mutations in genes encoding other complement regulatory proteins, membrane cofactor protein (CD46...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2006.08.004
更新日期:2007-03-01 00:00:00
abstract::Major histocompatibility complex (MHC) molecules present peptide antigens to T lymphocytes and initiate immune responses. The peptides loaded onto MHC class I or MHC class II molecules can be derived from cytosolic proteins, both self and foreign. A variety of cellular processes, including endocytosis, vesicle traffic...
journal_title:Molecular immunology
pub_type: 杂志文章,评审
doi:10.1016/j.molimm.2018.05.009
更新日期:2018-07-01 00:00:00
abstract::Protein kinases have been implicated in a number of regulatory mechanisms including signal transduction in many cells. To address the possibility that the large granular lymphocyte (LGL) also uses one or more unique protein kinases for LGL functions, an efficient method was developed to obtain partial cDNA clones for ...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(91)90153-b
更新日期:1991-04-01 00:00:00
abstract::Class switch DNA recombination (CSR) substitutes an immunoglobulin (Ig) constant heavy chain (C(H)) region with a different C(H) region, thereby endowing an antibody with different biological effector functions. CSR requires activation-induced cytidine deaminase (AID) and occurrence of double-strand DNA breaks (DSBs) ...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2008.07.003
更新日期:2008-11-01 00:00:00
abstract::Previous studies showed that P2 receptors are involved in neutrophil migration via stimulation of chemokine release and by facilitating chemoattractant gradient sensing. Here, we have investigated whether these receptors are involved in LPS-induced neutrophil transendothelial migration (TEM) using a Boyden chamber whe...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2009.11.020
更新日期:2010-02-01 00:00:00
abstract::Increasing indication is unveiling a role for poly(ADP-ribose) polymerase (PARP)-1 in the regulation of inflammatory/immune responses. The aim of the present study was to determine the potential anti-inflammatory effects of PARP-1 inhibitor 5-aminoisoquinolinone (5-AIQ) to explore the role of PARP-1 inhibitor in a mou...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2014.09.009
更新日期:2015-02-01 00:00:00
abstract::The 3-D complex structures of extracellular domain of human CD16 (FcgammaRIII) and hIgG1 or B88-9 were obtained by means of computer-guided molecular modeling, respectively. The binding epitopes were predicted and binding energy was calculated theoretically. The epitopes of human CD16 interacted with hIgG1 and B88-9 w...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2004.03.024
更新日期:2004-05-01 00:00:00
abstract::The purpose of the present work was to determine the ability of BgTX peptides, corresponding to the various loops and exposed regions of alpha-bungarotoxin (BgTX) and representing regions that are recognized by B and/or T cells, to stimulate protective immunity in mice against in vivo challenge with BgTX. The BgTX LD5...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(96)00014-4
更新日期:1996-05-01 00:00:00
abstract::The mucosal surface of the gastrointestinal tract represents a major entry point and ecological niche for many microbes. It forms an important immune barrier, absorbing nutrients, whilst preventing invasion by organisms. Of the extra-ordinarily diverse species that comprise the microbial world, relatively few organism...
journal_title:Molecular immunology
pub_type: 杂志文章,评审
doi:10.1016/j.molimm.2004.12.004
更新日期:2005-05-01 00:00:00
abstract::Mugwort (Artemisia vulgaris) belongs to the Compositae family, and is one of the main causes of allergy in late summer and autumn. The aim of the study was to characterize the allergen Art v 2 from mugwort pollen. Skin prick tests, performed in 19 patients allergic to mugwort and 10 control patients, showed an Art v 2...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2007.04.022
更新日期:2007-07-01 00:00:00
abstract:OBJECTIVE:Spinal cord injury (SCI) is a neurological disease with high incidence and disability. In this paper, we made a foundational study in long non-coding RNA paternally expressed gene 10 (lncRNA PEG10) at PC-12 cells. METHODS:We used CCK8, flow cytometry, migration and invasion assay to detect changes at the cel...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2019.11.012
更新日期:2020-02-01 00:00:00
abstract::We report that the protein tyrosine phosphatase PTP-PEST is expressed in resting human and mouse CD4(+) and CD8(+) T cells, but not in Jurkat T leukemia cells, and that PTP-PEST protein, but not mRNA, was dramatically downregulated in CD4(+) and CD8(+) primary human T cells upon T cell activation. This was also true i...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2008.03.019
更新日期:2008-06-01 00:00:00
abstract::Since secretion of IgE antibodies is known to be blocked by tunicamycin, the first aim of the present study was to determine at which step of glycosylation or processing secretion was restored. For this purpose, murine hybridoma cells secreting an anti beta-lactoglobulin IgE were incubated either in the presence of in...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(87)90187-8
更新日期:1987-08-01 00:00:00
abstract::Chagas' disease, caused by Trypanosoma cruzi, is an inflammatory disorder leading to chronic Chagas cardiomyopathy (CCC). Only one third of T. cruzi-infected individuals progress to CCC while the others are considered asymptomatic (ASY). The human inhibitory kappaB-like gene (IKBL/NFKBIL1), homologous to the IkappaB f...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2007.04.015
更新日期:2008-01-01 00:00:00
abstract::In Drosophila the synthesis of antimicrobial peptides in response to microbial infections is under the control of the Toll and immune deficiency (Imd) signaling pathways. The Toll signaling pathway responds mainly to Gram-positive bacterial and fungal infection while the Imd pathway mediates the response to Gram-negat...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2008.01.015
更新日期:2008-05-01 00:00:00
abstract::Selection of specific antibodies from large repertoires is of importance in generating antibodies to specific structural determinants and in studying structure-function relationships. Alkaline phosphatase (AP) has several isozymes with various degrees of homology and a range of common synthetic substrates. We have pre...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2006.02.024
更新日期:2007-01-01 00:00:00
abstract::Four cell lines producing monoclonal antibodies were obtained by fusion of NS1 myeloma cells with splenocytes of BALB/C mice immunized with only 1 microgram of each staphylococcal enterotoxin A, B, C1 and D by a modified technique of intrasplenic boosting. This procedure was considerably more efficient than the more c...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(87)90118-0
更新日期:1987-12-01 00:00:00
abstract::Aberrant O-glycosylation of cell surface mucin antigens is characteristic of epithelial cancer cells. For example, Thomsen-Friedenreich disaccharide (TFD) is a chemically well-defined carbohydrate antigen with a documented link to malignancy. There have been many attempts to improve immune response to carbohydrate ant...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/s0161-5890(01)00123-7
更新日期:2002-03-01 00:00:00
abstract::T-cell activation requires interaction of T-cell receptors (TCR) with peptide epitopes bound by major histocompatibility complex (MHC) proteins. This interaction occurs at a special cell-cell junction known as the immune or immunological synapse. Fluorescence microscopy has shown that the interplay among one agonist p...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2007.09.022
更新日期:2008-03-01 00:00:00
abstract::Bothropasin is a hemorrhagic snake venom metalloproteinase (SVMP) from Bothrops jararaca venom, the snake responsible for most bites in Southeastern Brazil. SVMPs, such as bothropasin, are involved in the main bothropic envenoming symptoms, which include hemorrhage, inflammation, necrosis and blood coagulation deficie...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2018.10.019
更新日期:2018-12-01 00:00:00
abstract::Activation of Jurkat T cells with phytohemagglutinin, CD3 or CD2 mAbs results in a marked inhibition of phosphatidylserine (PS) synthesis. Monitoring PS synthesis in T cells shows that: (i) after modulation of CD3 molecules the cells become refractory to further treatment with CD3 mAbs as well as to a further challeng...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(89)90072-2
更新日期:1989-11-01 00:00:00
abstract::Dendritic cells (DCs) are recruited to inflammatory sites where they phagocytose and process antigens for subsequent presentation to the T lymphocytes in the lymphoid tissue. Several leukocyte chemoattractants and their specific receptors have been shown to induce the migration of DC. The complement protein C1q has mu...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2005.07.030
更新日期:2006-03-01 00:00:00
abstract::The A/J murine hybridoma cell line 40-150 secretes antidigoxin antibodies with high affinity for digoxin. A first-order spontaneous mutant (40-150 A2.4) produces antibodies containing a mutation at heavy chain position 94 resulting in reduced affinity for digoxin. A second-order mutant (40-150 A2.4 P.10) derived from ...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(92)90010-u
更新日期:1992-04-01 00:00:00
abstract::Infectious salmon anaemia virus (ISAV) is a marine orthomyxovirus of significant interest not only as a cause of a fatal disease of farmed Atlantic salmon resulting in severe economic losses to the aquaculture industry, but also as the only poikilothermic orthomyxovirus. ISAV targets vascular endothelial cells and mac...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2009.06.015
更新日期:2009-09-01 00:00:00
abstract::We have previously shown that immunization with SIV-, SHIV-, or HA (influenza hemagglutinin)-virus-like particles (VLPs) elicits a strong humoral immune response in mice. However, little is known about the action VLPs exert on immune effector cells, including B cells. In this study, we found that all three types of VL...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2009.03.008
更新日期:2009-06-01 00:00:00