Abstract:
:We have previously generated human IgG1 antibodies that were engineered for reduced binding to the classical Fcγ receptors (FcγRI-III) and C1q, thereby eliminating their destructive effector functions (constant region G1Δnab). In their potential use as blocking agents, favorable binding to the neonatal Fc receptor (FcRn) is important to preserve the long half-life typical of IgG. An ability to cross the placenta, which is also mediated, at least in part, by FcRn is desirable in some indications, such as feto-maternal alloimmune disorders. Here, we show that G1Δnab mutants retain pH-dependent binding to human FcRn but that the amino acid alterations reduce the affinity of the IgG1:FcRn interaction by 2.0-fold and 1.6-fold for the two antibodies investigated. The transport of the modified G1Δnab mutants across monolayers of human cell lines expressing FcRn was approximately 75% of the wild-type, except that no difference was observed with human umbilical vein endothelial cells. G1Δnab mutation also reduced transport in an ex vivo placenta model. In conclusion, we demonstrate that, although the G1Δnab mutations are away from the FcRn-binding site, they have long-distance effects, modulating FcRn binding and transcellular transport. Our findings have implications for the design of therapeutic human IgG with tailored effector functions.
journal_name
Mol Immunoljournal_title
Molecular immunologyauthors
Stapleton NM,Armstrong-Fisher SS,Andersen JT,van der Schoot CE,Porter C,Page KR,Falconer D,de Haas M,Williamson LM,Clark MR,Vidarsson G,Armour KLdoi
10.1016/j.molimm.2018.01.006subject
Has Abstractpub_date
2018-03-01 00:00:00pages
1-9eissn
0161-5890issn
1872-9142pii
S0161-5890(18)30006-3journal_volume
95pub_type
杂志文章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::Increasing lines of evidence indicate that arsenic may be associated with immune related problems, but its detailed effects on immune organs are poorly understood. The objective of this study was to explore inflammatory responses and T cell differentiation of arsenic exposure in spleen and thymus. Female C57BL/6 mice ...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2016.12.005
更新日期:2017-01-01 00:00:00
abstract::The C-terminal domain of protein 4.1G was identified to interact with the cytosolic tail of the high affinity IgG receptor, Fc gamma RI, in yeast two-hybrid screens. Proteins of the 4.1 family have previously been found to mediate receptor/cytoskeleton interactions. In the study presented here, we show an alternativel...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2007.10.024
更新日期:2008-04-01 00:00:00
abstract::Leprosy is a bacterial disease caused by M. leprae. Its clinical spectrum reflects the host's immune response to the M. leprae and provide an ideal model to investigate the host pathogen interaction and immunological dysregulation. Tregs are high in leprosy patients and responsible for immune suppression of the host b...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2017.01.008
更新日期:2017-03-01 00:00:00
abstract::Mast cells have a clear-cut pathologic role in allergy, participating in a number of chronic inflammatory conditions, in helmintic parasitosis, and in some solid tumor reactions, but also in physiological situations, such as wound healing and innate immunity. Mast cells release a large number of proinflammatory, immun...
journal_title:Molecular immunology
pub_type: 杂志文章,评审
doi:10.1016/s0161-5890(02)00090-1
更新日期:2002-09-01 00:00:00
abstract::The structural and functional integrity of the cell is largely maintained by protein-protein interactions. Recently, we demonstrated that multiple antigenic peptides (MAPs) constructed from 60 kDa Ro sequence could be used to show intramolecular and intermolecular protein-protein interaction within the 60 kDa Ro ribon...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2004.03.036
更新日期:2004-07-01 00:00:00
abstract::When 5-fluorouracil (5-FU) resistant bone marrow (BM) cells are depleted of B-cells and then cultured in insert chambers [separated from a layer of adherent BM (aBM) cells by a nucleopore membrane], no mature, lipopolysaccharide (LPS) reactive B-cells are formed. Factors acting on B-cell precursors are not produced un...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(88)90146-0
更新日期:1988-11-01 00:00:00
abstract::In addition to classic Smad signaling pathways, the pleiotropic immunoregulatory cytokine TGF-beta1 can activate MAP kinases, but a role for TGF-beta1-MAP kinase pathways in T cells has not been defined heretofore. We have shown previously that TGF-beta1 inhibits Th1 development by inhibiting IFN-gamma's induction of ...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2007.02.024
更新日期:2007-07-01 00:00:00
abstract::The anti-inflammatory cytokine IL-10 is a key modulator of immune responses. A better understanding of the regulation of this cytokine offers the possibility of tipping the balance of the immune response toward either tolerance, or enhanced immune responses. Histone deacetylases (HDACs) have been widely described as n...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2014.02.019
更新日期:2014-07-01 00:00:00
abstract::The specificity of a mouse anti-testicular cell monoclonal antibody, J1, was investigated. Previous studies suggested that N-acetyl-D-glucosamine (GlcNAc) was a constituent of the determinant recognized by J1. When the antibody was tested against a variety of purified glycolipids containing this saccharide in terminal...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(84)90142-1
更新日期:1984-10-01 00:00:00
abstract::NKG2D receptor-ligand interaction triggers NK cell-mediated cytolysis and IFN-gamma secretion. IFN-gamma produced by NK cells has been found to promote the interaction between NK cells and monocytes; however, the underlying mechanism remains elusive. We demonstrate here that IFN-gamma exclusively induced or upregulate...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2007.10.007
更新日期:2008-03-01 00:00:00
abstract::Following measles virus (MV) infection, viral peptides are presented to CTL by MHC class I molecules on infected antigen presenting cells at widely different epitope densities. Whereas three MV epitopes (MV-M(211-219), MV-F(438-446) and MV-H(30-38)) derived from different structural proteins occur at regular densities...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/s0161-5890(02)00204-3
更新日期:2003-01-01 00:00:00
abstract::The paper evaluates the role of the concept of degeneracy in current immunology. The historical background of the notion is considered, as well as that of related concepts like 'cross-reactivity' and 'promiscuity'. A distinction is made between degeneracy, as a property of a system and promiscuity, as a property of an...
journal_title:Molecular immunology
pub_type: 杂志文章,评审
doi:10.1016/j.molimm.2003.11.021
更新日期:2004-02-01 00:00:00
abstract::Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (Mtb), leading to high mortality worldwide. It is well-established that cellular immunity plays a critical role to control Mtb infection. Dendritic Cells (DCs) are potent antigen presenting cells, which play an important role to prime cell...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2016.04.014
更新日期:2016-07-01 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::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 collection of epitopes present within the variable regions of the tumor-specific clonal immunoglobulin expressed by B cell lymphomas (idiotype, Id) can serve as a target for active immunotherapy. Traditionally, tumor-derived Id protein is chemically conjugated to the immunogenic foreign carrier protein keyhole lim...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2008.10.020
更新日期:2009-01-01 00:00:00
abstract::Affinity-purified major histocompatibility complex (MHC) class II molecules are known to bind antigenic peptides in vitro. The percentage of MHC class II molecules occupied with such peptides is usually very low and varies significantly depending upon the sequence and size of a given antigenic peptide. The present stu...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(94)90030-2
更新日期:1994-10-01 00:00:00
abstract::Idiotypic-like interactions between mAbs directed against cytidine (Cyd) or guanosine (Guo) nucleosides were characterized. These mAbs, Cyd-1 (IgG2b, kappa), Guo-1 (IgG1, kappa) and Guo-2 (IgG1, kappa) were derived from splenocytes of A/J mice immunized with Cyd-KLH or Guo-KLH and recognized the nucleoside base moieti...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(94)90139-2
更新日期:1994-01-01 00:00:00
abstract::A channel catfish genomic lambda library was screened with CH and JH probes which were derived from our earlier sequence analyses on different full-length heavy chain cDNA clones. One clone, designated C7, contained a genomic insert of about 18 kb and hybridized with specific probes for each of the four domains of the...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(92)90096-g
更新日期:1992-02-01 00:00:00
abstract::Traumatic brain injury (TBI) is a major cause of motor and cognitive impairment in young adults. It is associated with high mortality rates and very few effective treatment options. Bisperoxovanadium (pyridine-2-carboxyl) [bpV(pic)] is an commercially available inhibitor of Phosphatase and tensin homolog (PTEN). Previ...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2019.04.010
更新日期:2019-08-01 00:00:00
abstract::In the previous study, antibodies against CD3 molecule have been produced and were used in labeling T cells in Japanese flounder (Paralichthys olivaceus). In this paper, CD4+ and CD8+ lymphocytes subpopulations in peripheral blood leucocytes (PBL), spleen and head kidney of flounder were investigated. The flounder CD4...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2017.02.015
更新日期:2017-05-01 00:00:00
abstract::Although granulocyte colony-stimulating factor(G-CSF) has pathogenic roles in several immune inflammatory diseases, its role in periodontitis has not been investigated. Here we detected local expression of G-CSF using public datasets in the Gene Expression Omnibus (GEO) database, and immune cell infiltration into ging...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2019.11.003
更新日期:2020-01-01 00:00:00
abstract::Glycosylation is an important protein post-translational modification. In this process, the intermediate product, Tn antigen, arises from somatic mutations in core1β3-galactosyltransferase-specific molecular chaperone (Cosmc), which is required for the formation of active core1β3-galactosyltransferase (T-synthase). As...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2017.06.250
更新日期:2017-10-01 00:00:00
abstract::A monoclonal human IgG1, Campath-1H, was digested with glycosidases to assess the effect of carbohydrate on the functional activities of an IgG1. Removal of the complete carbohydrate moiety abolished complement lysis activity and antibody-dependent cell-mediated cytotoxicity, but left antigen binding activity and prot...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(95)00118-2
更新日期:1995-12-01 00:00:00
abstract::Here we present the gene structure and expression data on two Atlantic salmon TNF-alpha genes. Both genes are approximately 2.0kb in length and organized into four exons and three introns. The open reading frame of both genes translates into 246 amino acid putative peptides, being 91.5% identical at the amino acid lev...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2006.08.015
更新日期:2007-03-01 00:00:00
abstract::The binding properties of 18 monoclonal antibodies (MAbs) directed against the tobacco mosaic virus (TMV) coat protein were studied with five related tobamoviruses and seven mutant viruses, as well as with the dissociated coat proteins of these variants. Ten of the antibodies bound to both TMV and TMV protein, but the...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(87)90131-3
更新日期:1987-12-01 00:00:00
abstract::Peripheral blood B lymphocytes have been isolated from healthy individuals who were immunized with lymphocytes from HLA-incompatible donors and transformed with Epstein-Barr virus to produce human monoclonal cell lines specific for human HLA molecules. The cell lines have been previously characterized and are known to...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(95)00071-2
更新日期:1995-10-01 00:00:00
abstract::Hepatitis B virus (HBV) infection afflicts over 350 million people worldwide and is a leading cause of hepatitis, cirrhosis and hepatocellular carcinoma. HBV replicates noncytopathically in hepatocytes, and most of the hepatic injury is caused by the immune response to the virus. While most studies focused on the adap...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/j.molimm.2009.09.022
更新日期:2009-12-01 00:00:00
abstract::A procedure to quantitate the immunogenic potential of protein antigens is presented. It is hypothesized that the intrinsic immunogenicity of an accessible region on the protein arises from the overall structural effect of the presence of the particular assemblage of amino acid residues in the given region. Structural...
journal_title:Molecular immunology
pub_type: 杂志文章
doi:10.1016/0161-5890(85)90043-4
更新日期:1985-11-01 00:00:00