• A much more promising strategy is to use recombinant monoclonal antibodies (mAbs) against influenza and several are currently in clinical development ( 9 - 13 ). (frontiersin.org)
  • Methods Monoclonal antibodies recognising the fibrinogen-like globe (FBG) of tenascin-C were generated by phage display. (bmj.com)
  • In this work, we evaluated a panel of 16 anti-BoNT/A monoclonal antibodies (mAbs) for their ability to inhibit the in vitro activity of BoNT/A1, /A2, and /A3 complex as well as the recombinant LC of A1. (cdc.gov)
  • To enable rational antigen design, we solved a cryo-EM structure of the highly potent anti-PfCSP antibody L9 in complex with recombinant PfCSP. (nature.com)
  • and monoclonal recombinant antibodies are also currently being pursued for prevention of HIV-1 infection in large Phase IIb clinical trials (NTC02716675 and NCT02568215). (frontiersin.org)
  • Antibodies are heavy (~150 k Da ) proteins of about 10 nm in size, [7] arranged in three globular regions that roughly form a Y shape. (wikipedia.org)
  • The production of antibody fragments and antibody fusion proteins by yeasts and filamentous fungi. (scriptiebank.be)
  • These proteins contain two related domains known as the chromo- and the chromoshadow-domain. (cipsm.de)
  • In addition, we identified proteins that interact with the KRAB domain of PRDM9 in yeast two-hybrid assay screens, particularly CXXC1, a member of the COMPASS complex. (springer.com)
  • Synaptic vesicle exocytosis occurs at specialized regions of the presynaptic membrane, termed active zones, in which presynaptic release machinery proteins cluster opposite postsynaptic neurotransmitter receptors. (jneurosci.org)
  • We have previously described R1a-B6, an alpaca-derived single domain antibody (nanobody), that is capable of potent cross-subtype neutralization in vitro of H1N1, H5N1, H2N2, and H9N2 influenza viruses, through binding to a highly conserved epitope in the influenza hemagglutinin stem region. (frontiersin.org)
  • [2] [3] Each tip of the "Y" of an antibody contains a paratope (analogous to a lock) that is specific for one particular epitope (analogous to a key) on an antigen, allowing these two structures to bind together with precision. (wikipedia.org)
  • The antigen-binding regions of each Fab retain their ability to bind to the epitope for which they are specific. (equimount.com)
  • These rare mAbs bind to functionally conserved epitopes such as those in the hemagglutinin (HA) stem, thereby providing strain independent protection. (frontiersin.org)
  • The mAbs binding the C-terminal portion of the BoNT/A heavy chain had optimal properties for use in the Endopep-MS assay. (cdc.gov)
  • Continuous cultures of fused cells secreting antibody of predefined specificity. (scriptiebank.be)
  • 2012 ), generalizing the observation that hotspot localization is determined by the DNA-binding specificity of the zinc finger array (Grey et al. (springer.com)
  • These Fc receptor-dependent antibody functions provide a direct link between the innate and adaptive immune systems by combining the potent antiviral activity of innate effector cells with the diversity and specificity of the adaptive humoral response. (frontiersin.org)
  • To allow the immune system to recognize millions of different antigens, the antigen-binding sites at both tips of the antibody come in an equally wide variety. (wikipedia.org)
  • Accordingly, there remains a need for antibodies that do not provoke a strong immune response but yet bind strongly to their antigens and methods for identifying such antibodies. (justia.com)
  • cells are activated by interaction with antigens and obtain T indicated that the cell lines representing a defined cell help, they mature into terminally differentiated plasma stage generally presented a high similarity in over- cells secreting large amounts of antibodies [10 -12]. (lu.se)
  • The antibody recognizes a unique molecule of the pathogen, called an antigen . (wikipedia.org)
  • The class hence determines the function triggered by an antibody after binding to an antigen, in addition to some structural features. (wikipedia.org)
  • After an antigen binds to a BCR, the B cell activates to proliferate and differentiate into either plasma cells , which secrete soluble antibodies with the same paratope, or memory B cells , which survive in the body to enable long-lasting immunity to the antigen. (wikipedia.org)
  • The antigen binding site is circled. (wikipedia.org)
  • Structurally an antibody is also partitioned into two antigen-binding fragments (Fab), containing one V L , V H , C L , and C H 1 domain each, as well as the crystallisable fragment (Fc), forming the trunk of the Y shape. (wikipedia.org)
  • The invention relates to methods of modulating the antigen-binding affinity of an antibody by determining, using data corresponding to the structure of a complex between the antibody and an antigen in a solvent, a representation of a charge distribution of the CDRs of the antibody which minimizes electrostatic contribution to binding free energy between the antibody and the antigen in a solvent. (justia.com)
  • Guided by these determinations, the antibody is accordingly modified (altered) to improve upon, e.g., antibody/antigen binding by modifying at least one amino acid residue to decrease the binding free energy between the antibody and antigen when bound in a solvent. (justia.com)
  • The variable domains of each pair of light and heavy chains form the site that comes into contact with an antigen. (justia.com)
  • The CDRs of V H and V L are held in close proximity by the FRs, and amino acid residues within the CDRs bind the antigen. (justia.com)
  • Researchers hoped that such antibodies would be no more foreign to the human body than a genuine human antibody, but the utility of such antibodies has been restricted, at least in some cases, by a reduction in the antibody's affinity for the antigen. (justia.com)
  • Antiviral activities of antibodies may either be dependent only on interactions between the antibody and cognate antigen, as in binding and neutralization of an infectious virion, or instead may require interactions between antibody-antigen immune complexes and immunoproteins or Fc receptor expressing immune effector cells. (frontiersin.org)
  • The Fc receptor-dependent function of antibody-dependent cellular phagocytosis (ADCP) provides mechanisms for clearance of virus and virus-infected cells, as well as for stimulation of downstream adaptive immune responses by facilitating antigen presentation, or by stimulating the secretion of inflammatory mediators. (frontiersin.org)
  • Some functions, such as neutralization, mainly depend on interaction of the Fv domain ( Figure 1A ) with antigen and are therefore predominantly Fc domain independent. (frontiersin.org)
  • Fc receptor-dependent antibody functions are also involved in activation of downstream adaptive immune responses by facilitating antigen presentation or by stimulating the secretion of inflammatory mediators ( 12 , 13 ). (frontiersin.org)
  • Our findings demonstrate that a single intramuscular injection in mice of AAV encoding R1a-B6 fused to Fc fragments of different isotypes equipped either, with or without antibody dependent cellular cytotoxicity (ADCC) activity, was able to drive sustained high-level expression (0.5-1.1 mg/mL) in sera with no evidence of reduction for up to 6 months. (frontiersin.org)
  • A method based on atomic force microscopy is used to delineate the properties that determine single-molecule adhesion onto solid substrates in aqueous environment. (cipsm.de)
  • Antibodies are exquisite, naturally occurring biological agents that play a critical role in defending the body from pathogens. (justia.com)
  • Fc receptor-dependent antibody functions are important components of the immune response that provide mechanisms for clearance of infected host cells, immune complexes, or opsonized pathogens. (frontiersin.org)
  • In this review, we discuss the properties of Fc receptors, antibodies, and effector cells that influence ADCP. (frontiersin.org)
  • In addition, larvae containing mutations in both RIM and rab3 have reduced Ca 2+ channel levels and a Brp distribution that is very similar to that of the rab3 single mutant, indicating that RIM functions to regulate Ca 2+ channel accumulation but is not a Rab3 effector for release machinery distribution across release sites. (jneurosci.org)
  • In rodents and C. elegans , RIM binds to and is an effector of the small GTPase Rab3. (jneurosci.org)
  • Together with B and T cells , antibodies comprise the most important part of the adaptive immune system . (wikipedia.org)
  • Antibodies are a key component of the human adaptive immune system, and the elicitation of antibodies has been correlated with vaccine efficacy in many diseases ( 1 ). (frontiersin.org)
  • The chromo-domain binds histone H3 tails methylated on lysine 9. (cipsm.de)
  • This role involves its DNA-binding domain, which is composed of a tandem array of zinc fingers, and PRDM9-dependent trimethylation of histone H3 at lysine 4. (springer.com)
  • 2010 ). PRDM9 includes several functional domains, such as a DNA-binding zinc finger array, a histone lysine methyltransferase PR/SET (PRDI-BF1 and RIZ1 homology) domain, and a Krüppel-associated box (KRAB)-related domain. (springer.com)
  • Because these fluids were traditionally known as humors , antibody-mediated immunity is sometimes known as, or considered a part of, humoral immunity . (wikipedia.org)
  • We propose that additional investigation into the role of ADCP in protective viral responses, the specific virus epitopes targeted by ADCP antibodies, and the types of phagocytes and Fc receptors involved in ADCP at sites of virus infection will provide insight into strategies to successfully leverage this important immune response for improved antiviral immunity through rational vaccine design. (frontiersin.org)
  • The overall objective of EuroNeut-41 was to design a vaccine that raises antibodies able to prevent HIV cell fusion by blocking the virus fusion protein gp41 in its pre-fusogenic conformation. (europa.eu)
  • A primary objective in malaria vaccine design is the generation of high-quality antibody responses against the circumsporozoite protein of the malaria parasite, Plasmodium falciparum (PfCSP). (nature.com)
  • Using in vitro and cellular techniques, we present a mVP40 assembly model highlighting two distinct oligomerization interfaces: the (N-terminal domain (NTD) and C-terminal domain (CTD)) in mVP40. (uci.edu)
  • fragment contains a region that binds to the cellular Fc receptor. (equimount.com)
  • An antibody ( Ab ), also known as an immunoglobulin ( Ig ), [1] is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses . (wikipedia.org)
  • Antibodies are glycoproteins belonging to the immunoglobulin superfamily . (wikipedia.org)
  • The terms antibody and immunoglobulin are often used interchangeably, [1] though the term 'antibody' is sometimes reserved for the secreted, soluble form, i.e. excluding B-cell receptors. (wikipedia.org)
  • 1) Antibody deficiency disorders are defects in immunoglobulin-producing B cells . (lu.se)
  • Antibody deficiencies are treated with intravenous immunoglobulin substitution therapy. (lu.se)
  • regions (CDRs) of the VH and VL chains are shown in this fragment. (equimount.com)
  • There is clearly an urgent need for additional approaches and antibodies present new opportunities for both therapeutic and prophylactic intervention. (frontiersin.org)
  • Therapeutic antibodies for human diseases at the dawn of the twenty-first century. (scriptiebank.be)
  • Researchers have modified antibodies in various ways in order to study their function or to improve their utility as therapeutic agents. (justia.com)
  • We found that L9 Fab binds multivalently to the minor (NPNV) repeat domain, which is stabilized by a unique set of affinity-matured homotypic, antibody-antibody contacts. (nature.com)
  • In combination with MD simulations, these data indicate a key role in affinity-matured homotypic contacts in the L9 light chain for mediating high-affinity PfCSP binding and potent protection from malaria infection. (nature.com)
  • Since S-layers rapidly growing scientific and engineering discipline that are composed of a single protein or glycoprotein species crosses the boundaries of numerous existing fields. (2medicalcare.com)
  • Here, we report OTUD3 (OTU domain-containing protein 3) functions as a deubiquitylase for IRP2, interacts with IRP2 in the cytoplasm, de-polyubiquitylates, and stabilizes IRP2 protein in an iron-independent manner. (nature.com)
  • Here we report the selection of camelid-derived single-domain antibodies (nanobodies) that modulate the conformation and spectral properties of the green fluorescent protein (GFP). (cipsm.de)
  • PR domain-containing protein 9 (PRDM9) is a major regulator of the localization of meiotic recombination hotspots in the human and mouse genomes. (springer.com)
  • PRDM9 is a member of the PRDM family of transcription regulators, but unlike other family members, it contains a Krüppel-associated box (KRAB)-related domain that is predicted to be a potential protein interaction domain. (springer.com)
  • One pathway, which has been extensively studied in yeast, is mainly guided by chromatin structure and the other, analyzed in detail in mice, is driven by the sequence-specific DNA-binding PR domain-containing protein 9 (PRDM9). (springer.com)
  • FLIM-FRET analysis of protein-protein interactions showed that PLIN5 S155 phosphorylation regulates PLIN5 interaction with adipose triglyceride lipase at the lipid droplet, but not with α-β hydrolase domain-containing 5. (uci.edu)
  • these antibodies inhibit cytokine release by RA synovial cells and prevent disease progression and tissue destruction during collagen-induced arthritis. (bmj.com)
  • Because some antibodies inhibit or neutralize the activity of BoNT, the choice of antibody with which to extract the toxin is critical. (cdc.gov)
  • Initially, all antibodies are of the first form, attached to the surface of a B cell - these are then referred to as B-cell receptors (BCR). (wikipedia.org)
  • In some of the earliest modifications, researchers used double-stranded DNA sequences to express the V H or V L domains, but none of the sequence of the constant region (see, e.g. (justia.com)
  • B cells are therefore particularly dependent on 'quality control' mechanisms to oversee antibody production. (cipsm.de)
  • Using this binding mechanism, an antibody can tag a microbe or an infected cell for attack by other parts of the immune system, or can neutralize it directly (for example, by blocking a part of a virus that is essential for its invasion). (wikipedia.org)
  • The constant region at the trunk of the antibody includes sites involved in interactions with other components of the immune system. (wikipedia.org)
  • Antibodies from different classes also differ in where they are released in the body and at what stage of an immune response. (wikipedia.org)
  • Schematic structure of an antibody: two heavy chains (blue, yellow) and the two light chains (green, pink). (wikipedia.org)
  • Antibodies, which are also commonly referred to as immunoglobulins, contain four polypeptides: two longer polypeptides ("heavy chains") that are identical to one another and two shorter polypeptides ("light chains") that are identical to one another. (justia.com)
  • The heavy chains are paired with the light chains by disulfide bonds, and the two heavy chains are similarly bound to one another to create a tetrameric structure. (justia.com)
  • Moreover, the heavy and light chains each contain a variable domain and one or more constant regions: the heavy chain includes one variable domain (V H ) followed by three constant regions (C 1 H, C 2 H, and C 3 H), and the light chain includes one variable domain (V L ) followed by a single constant region (C L ). (justia.com)
  • We demonstrate that L9 utilizes a distinct homotypic interface to stabilize multivalent Fab binding to the PfCSP minor repeats, and a unique paratope structure to selectively interact with NPNV repeats. (nature.com)
  • We have previously reported the effectiveness of antibody-capture to purify and concentrate BoNTs from complex matrices, such as clinical samples. (cdc.gov)
  • The most promising Ags were submitted to a more in-depth biophysical investigation of their structure and conformation stability, and for their capacity to interact with neutralising antibodies (Abs) and peptides. (europa.eu)
  • Recently, Np95 (also known as UHRF1 or ICBP90) has been found to interact with Dnmt1 and to bind hemimethylated DNA, indicating together with genetic studies a central role in the maintenance of DNA methylation. (cipsm.de)
  • represent the only wall component and can be so closely One of the great challenges for nano(bio)technology is associated with the plasma membrane that a hydrophobic the creation of supramolecular materials in which the domain of the constituent subunits is actually integrated into constituent units are highly regular molecular nanostructures. (2medicalcare.com)
  • In most Gram-positive bacteria the Thus, learning how to create complex and large supra- S-layer is attached to a rigid wall matrix involving lectin molecular structures and the elucidation of rules mediating binding between a glycan (referred to as secondary cell wall their organization into functional materials will offer a broad polymer, SCWP) covalently-attached to the peptidoglycan spectrum of new technologies. (2medicalcare.com)
  • B cells use unconventional strategies for the production of a seemingly unlimited number of antibodies from a very limited amount of DNA. (cipsm.de)
  • Anti-FBG antibodies inhibited cytokine release by RA synovial cells and prevented disease progression and tissue destruction during collagen-induced arthritis. (bmj.com)
  • 3) T cell deficiencies result usually in combined immunodeficiencies (CIDs), where both T cells and antibody production are defective. (lu.se)
  • The heavy chain is responsible for both receptor some species of the genus Clostridium, in particular, Clostridium binding via its C-terminal (CT) binding domain [4,5] (HC) and botulinum, C. butyricum, C. baratii, and C. argentinense. (cdc.gov)
  • Under various iron conditions, IRPs could bind to IREs in the targeted mRNA, stabilize the mRNA or prevent its translation. (nature.com)
  • In the past dozen years, the outbreak of the novel coronavirus is the third on record spillover of an animal coronavirus to humans after occurring of severe acute respiratory syndrome (SARS) started in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2014, which is resulting in a pandemic in global. (medsci.org)
  • Their simple modular structure and single open reading frame format are highly amenable to gene therapy-mediated delivery. (frontiersin.org)
  • A more practical and cost-effective strategy would be to use antibody gene therapy which would provide long term sustainable protection through antibody production within the patient. (frontiersin.org)
  • In Saccharomyces cerevisiae , meiotic DSBs preferentially occur at nucleosome-depleted regions in gene promoters (Ohta et al. (springer.com)
  • Antibodies can exert their protective functions via a multitude of mechanisms. (frontiersin.org)
  • Other specific initiatives were conducted such as evaluation of the sublingual route for immunization, investigation of the Principal Immunodominant Domain (PID) of gp41, and direct HIV inhibition with an Ag family which demonstrated in vitro antiviral activities comparable to the antiretroviral drug T20 (Fuzeon). (europa.eu)
  • A more accurate depiction of an antibody (3D structure at RCSB PDB ). (wikipedia.org)
  • The DEC-205 monomer forms a compact structure comprising two intercalated rings of C-type lectin-like domains, where the N-terminal cysteine-rich and fibronectin domains reside at the central intersection. (uci.edu)
  • More detailed accounts of the structure of variable domains can be found in Poljak et al. (justia.com)
  • 2009 ). At a larger scale, DSB formation occurs in the context of a specific chromosome architecture that consists of chromatin loops anchored to a proteinaceous axis (Zickler and Kleckner 1999 ). (springer.com)
  • Intoxication with delivering the catalytic light chain (LC) to its target via its N- one of the seven distinct serotypes of BoNT (A-G) causes botulism, terminal translocation domain (HN) [6]. (cdc.gov)
  • Passive transfer of serum antibodies from convalescent patients has been used in the past ( 7 , 8 ), however, this approach is of limited use in a global pandemic emergency. (frontiersin.org)
  • Antibodies stained synovial biopsies of patients at different stages of RA development. (bmj.com)
  • Patients with antibody deficiencies are especially susceptible to encapsulated bacteria, which cause pyogenic infections. (lu.se)
  • Here, we show that truncation of the KRAB domain of mouse PRDM9 leads to loss of PRDM9 function and altered meiotic prophase and gametogenesis. (springer.com)
  • Induction of binding Abs was measured by ELISA and neutralizing activity by PBMC and TZM-bl assays in all serum and vaginal samples. (europa.eu)
  • Another design strategy was developed using gammaretroviruses backbone where 2 domains were substituted with HIV epitopes in the N-terminal part of the ectodomain and the membrane proximal external region (MPER) respectively. (europa.eu)
  • The protease not only releases small peptides, such as the amyloid-β peptide, which drives Alzheimer's disease pathogenesis, but also intracellular domains, which can have critical functions in nuclear signaling. (cipsm.de)
  • Indeed, in the absence of PRDM9, meiotic DSBs occur at transcription regulatory regions, such as promoters and enhancers (Brick et al. (springer.com)
  • Cross-subtype neutralizing single domain antibodies against influenza present new opportunities for immunoprophylaxis and pandemic preparedness. (frontiersin.org)
  • Five single nucleotide polymorphism mutations of OTUD3 are present in cases of sporadic PD or controls, although no significant associations of OTUD3 SNPs with sporadic PD are detected. (nature.com)