Abstract:
:Bacterial lipopolysaccharide (LPS) activates the innate immune system by forming a complex with myeloid differentiation factor 2 (MD-2) and Toll-like receptor 4 (TLR4), which is present on antigen presenting cells. MD-2 plays an essential role in this activation of the innate immune system as a member of the ternary complex, TLR4:MD-2:LPS. With the goal of further understanding the molecular details of the interaction of MD-2 with LPS and TLR4, and possibly toward engineering dominant negative regulators of the MD-2 protein, here we subjected MD-2 to a mutational analysis using yeast display. The approach included generation of site-directed alanine mutants, and ligand-driven selections of MD-2 mutant libraries. Our findings showed that: (1) proline mutations in the F119-K132 loop that binds LPS were strongly selected for enhanced yeast surface stability, (2) there was a preference for positive-charged side chains (R/K) at residue 120 for LPS binding, and negative-charged side chains (D/E) for TLR4 binding, (3) aromatic residues were strongly preferred at F119 and F121 for LPS binding, and (4) an MD-2 mutant (T84N/D101A/S118A/S120D/K122P) exhibited increased binding to TLR4 but decreased binding to LPS. These studies revealed the impact of specific residues and regions of MD-2 on the binding of LPS and TLR4, and they provide a framework for further directed evolution of the MD-2 protein.
journal_name
Mol Immunoljournal_title
Molecular immunologyauthors
Mattis DM,Chervin AS,Ranoa DR,Kelley SL,Tapping RI,Kranz DMdoi
10.1016/j.molimm.2015.08.008subject
Has Abstractpub_date
2015-12-01 00:00:00pages
203-12issue
2 Pt Aeissn
0161-5890issn
1872-9142pii
S0161-5890(15)30057-2journal_volume
68pub_type
杂志文章abstract::Mycobacterium leprae, the causative agent of leprosy, challenges host defense mechanism by impairing the signal transduction of T cells which leads to downregulation of T cell proliferation, mainly as a consequence of interference with IL-2 production. In this study we sought to identify how soluble forms of M. leprae...
journal_title:Molecular immunology
pub_type: 临床试验,杂志文章
doi:10.1016/j.molimm.2006.09.008
更新日期:2007-03-01 00:00:00
abstract::MAIT cells are innate-like T cells that are enriched in mucosal sites and tissues including adipose tissue and liver. They play an important role in immunity against microbial pathogens. Recently, it has been reported that MAIT cells could also be important in metabolic diseases and can be involved in setting up and m...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2020.12.014
更新日期:2021-02-01 00:00:00
abstract::Major histocompatibility complex (MHC) has a profound influence on disease resistance or susceptibility, productivity and important economic traits in chicken. Association of the MHC with a wide range of immune responses makes it a valuable predictive factor for the disease pathogenesis and outcome. The tandem repeat ...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2017.06.027
更新日期:2017-10-01 00:00:00
abstract::T cells play a crucial role in the pathogenesis of most autoimmune disorders. However, target antigens and pathomechanisms leading to human autoimmune diseases are still largely unknown. Cross-recognition of T cells between self and foreign antigens has been considered as a driving force in generating autoimmunity. He...
journal_title:Molecular immunology
pub_type: 杂志文章,评审
doi:10.1016/j.molimm.2003.11.012
更新日期:2004-02-01 00:00:00
abstract::Tunicamycin inhibited the synthesis of glycosylated mu-chains and kappa-chains in the human lymphoblastoid cell line, Daudi. Nonglycosylated IgM could not be detected on the surface of tunicamycin-treated cells by cell surface iodination techniques even under conditions where membrane IgM was re-expressed in control c...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(83)90106-2
更新日期:1983-01-01 00:00:00
abstract::Mycobacterium tuberculosis (M.tb) infects 8 million and kills 2.2 million people each year worldwide. M.tb modulates the immune response of the infected individual. Empirically, suppressor carbohydrates (SC) produced by CD8+ T cells in response to M.tb were found to induce a T helper 2 response rather than a protectiv...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2007.10.022
更新日期:2008-03-01 00:00:00
abstract::Artificial Salmonella serogroup B, D or Cl-specific glycolipids were prepared by covalently linking oligosaccharides corresponding to two O-antigen repeating units, obtained by phage enzyme hydrolysis of native O-antigenic polysaccharides, to octyl residues. Sheep erythrocytes coated with the artificial glycolipids we...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(90)90152-p
更新日期:1990-09-01 00:00:00
abstract::Previous work from our laboratories has demonstrated that purified, recombinant human astrovirus coat protein (HAstV CP) binds C1q and mannose-binding lectin (MBL) inhibiting activation of the classical and lectin pathways of complement, respectively. Analysis of the 787 amino acid CP molecule revealed that residues 7...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2010.07.012
更新日期:2010-11-01 00:00:00
abstract::A cDNA clone, designated sbIL-6 (seabream interleukin-6), was obtained from a cDNA library of enriched immune-stimulated sequences from gilthead seabream. The deduced sbIL-6 protein corresponds to a 225-amino acid protein with a putative 24-amino acid signal peptide, four conserved alpha helices and one N-linked glyco...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2008.04.012
更新日期:2008-07-01 00:00:00
abstract::The variables regions of three syngeneic anti-idiotypic antibodies (Ab2s) were cloned and sequenced. They are encoded by different VL genes, two are from different members of V kappa-Ox1 superfamily. The H chains are encoded by VH genes belonging to three different VH families, J558, Q52 and 7183. Together with a prev...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(92)90045-y
更新日期:1992-09-01 00:00:00
abstract::Fibroblast-like synoviocyte (FLS) is the ultimate effectual cells in the pathogenesis of rheumatoid arthritis (RA). The current study was undertaken to investigate whether a proliferation-inducing ligand (APRIL) mediates the function of FLS in an animal model of RA. Rat adjuvant-induced arthritis (AA) was induced by i...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2014.11.002
更新日期:2015-03-01 00:00:00
abstract::A recent publication in Molecular Immunology by Leo and Goldman doi:10.1016/j.molimm.2009.02.024 has shown that the Escherichia coli immunoglobulin-binding (Eib) proteins are receptors for IgG and IgA. We would like to highlight important issues that were not addressed in their recent manuscript whilst providing possi...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2009.04.023
更新日期:2009-07-01 00:00:00
abstract::Immunization of different mice strains with a recombinant fusion protein composed of the vector-encoded N-terminal leader peptide CroLac (containing lambda Cro and LacI fragments) and a part of the transmembrane protein of HIV-1 (gp41) led to a high anti-CroLac humoral immune response. A detailed analysis of this resp...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(93)90144-z
更新日期:1993-06-01 00:00:00
abstract::The effect of antibody affinity on molecular forms of immune complexes was investigated by measuring antigen-antibody interactions using surface plasmon resonance (SPR), electrospray ionization time-of-flight mass spectrometry under non-denaturing conditions (MS), analytical ultracentrifugation (AUC), and transmission...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2009.09.009
更新日期:2009-12-01 00:00:00
abstract::Whether bovine myelin basic protein (BP) and bovine spinal cord protein (SCP) cross-react at the humoral immune level was assessed with a sensitive solid-phase enzyme immunoassay. We found that a hyperimmune anti-SCP serum reacted strongly with SCP and cross-reacted nearly as well with BP. A hyperimmune anti-BP serum ...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(84)90159-7
更新日期:1984-10-01 00:00:00
abstract::REV1 plays a key role in vertebrate translesion synthesis. Although its deoxycytidyl transferase activity is dispensable for tolerance of DNA damage caused by a number of mutagens, its extreme C terminus, which interacts with other translesion polymerases and PCNA, is essential. By examining immunoglobulin diversifica...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2005.09.017
更新日期:2006-04-01 00:00:00
abstract:BACKGROUND:The complement system is well known for its role in innate immunity via the classical, the alternative and the lectin pathways, although recent investigations suggest expanding roles in adipose tissue. Properdin stabilizes C3 convertase following alternative complement activation. Properdin is also present i...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2012.02.110
更新日期:2012-05-01 00:00:00
abstract::Most studies of the immune responses in allergic rhinitis have focused on IgE antibodies to mixtures of allergenic proteins. Based on our previous studies of the major mountain cedar allergen Jun a 1, we sought to describe a broader assessment of the humoral immune responses to a single, dominant allergen, in three gr...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2018.08.007
更新日期:2018-09-01 00:00:00
abstract::The outer membrane protein A (OmpA) is one of the intra-species conserved proteins with immunogenicity widely found in the family of Enterobacteriaceae. Here we first confirmed OmpA is conserved in the three pathogenic Yersinia: Yersinia pestis, Yersinia pseudotuberculosis and pathogenic Yersinia enterocolitica, with ...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2015.09.016
更新日期:2015-12-01 00:00:00
abstract::Cleavage by the proteasome is responsible for generating the C terminus of T-cell epitopes. Modeling the process of proteasome cleavage as part of a multi-step algorithm for T-cell epitope prediction will reduce the number of non-binders and increase the overall accuracy of the predictive algorithm. Quantitative matri...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2005.12.013
更新日期:2006-05-01 00:00:00
abstract::The globular C1q heterotrimer is a subunit of the C1 complement factor. Binding of the C1q subunit to the constant (Fc) part of antibody molecules is a first step and key event of complement activation. Although three-dimensional structures of C1q and antibody Fc subunits have been determined experimentally no atomic ...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2012.02.111
更新日期:2012-05-01 00:00:00
abstract::Immunoglobulins (Ig) require correct folding and assembly of both heavy (H) and light (L) chains to form a functional H2L2 dimer that is secreted from plasma cells. This process is dependent upon the endoplasmic reticulum (ER) chaperone BiP, which targets improperly, folded or assembled Ig molecules for degradation. W...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2004.11.015
更新日期:2005-05-01 00:00:00
abstract::The architecture of lymphoid microenvironments depends upon complex interactions between several stromal cell types. We describe in this report the cloning of a cDNA which encodes a novel membrane molecule containing two external Ig-like domains. It is expressed at the junction between endothelial cells including HEV....
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/s0161-5890(98)00102-3
更新日期:1998-12-01 00:00:00
abstract::GRX1 (glutaredoxin1), a sulfhydryl disulfide oxidoreductase, is involved in many cellular processes, including anti-oxidation, anti-apoptosis, and regulation of cell differentiation. However, the role of GRX1 in the oxidative stress and apoptosis of osteoarthritis chondrocytes remains unclear, prompting the current st...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2017.08.006
更新日期:2017-10-01 00:00:00
abstract::Membrane immunoglobulins are integral proteins on B cell surfaces that bind foreign antigens and are critically involved in the regulation of the immune response. Based upon the model of serum IgG, it has been assumed that membrane immunoglobulins are essentially four chain disulfide-linked structures of the form H2L2...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(93)90451-g
更新日期:1993-12-01 00:00:00
abstract::Subunits of the mitochondrial ATP synthase complex are expressed on the surface of tumors, bind the TCR of human Vgamma9/Vdelta2 lymphocytes and promote their cytotoxicity. Present experiments show that detection of the complex (called ecto-F1-ATPase) at the cell surface by immunofluorescence correlates with low MHC-c...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2007.05.026
更新日期:2008-01-01 00:00:00
abstract::To test the fate of developing B cells with autoreactive receptor components, we studied mice homozygous for a knock-in transgene coding the VH domain of an IgM ssDNA-binding antibody. The transgene has unmutated C57 BL/6 V gene segments. Homozygous knock-in mice developed normal numbers of spleen and bone marrow B ce...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2005.01.010
更新日期:2005-08-01 00:00:00
abstract::Intravenous drug use has become the principal route of hepatitis C virus (HCV) transmission due to the sharing of infected needles. In this study, we analyzed the distribution of HLA-KIR genotypes among 160 Puerto Rican intravenous drug users (IDUs) with HCV infection and 92 HCV-negative Puerto Rican IDUs. We found a ...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2009.05.014
更新日期:2009-08-01 00:00:00
abstract::To investigate the IL-6/IL-6 receptor system, we obtained five murine monoclonal antibodies against human IL-6, which neutralize its biological activity. We classified them into two groups (Type I mAb and Type II mAb) according to the epitopes they recognized. These two types of antibodies showed no difference in the ...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(91)90001-z
更新日期:1991-11-01 00:00:00
abstract:BACKGROUND:Ethanol feeding in mice activates complement via C1q binding to apoptotic cells in the liver; complement contributes to ethanol-induced inflammation and injury. Despite the critical role of C1q in ethanol-induced injury, the mechanism by which ethanol activates C1q remains poorly understood. Secretory IgM (s...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2016.02.008
更新日期:2016-04-01 00:00:00