The biological significance of specific antibody IgG subclass profiles.
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Animals↗
Biomedical subjects
M R Walker
Publications and source records attributed to M R Walker.
Comparison of the effector functions of human immunoglobulins using a matched set of chimeric antibodies.
Cell lines have been established that secrete a matched set of human chimeric IgM, IgG1, IgG2, IgG3, IgG4, IgE, and IgA2 antibodies that are directed against the hapten 4-hydroxy-3-nitrophenacetyl. These chimeric antibodies secreted from mouse plasmacytoma cells behave exactly like their authentic human counterparts in SDS-PAGE analysis, binding to protein A and in a wide range of serological assays. The antibodies have been compared in their ability to bind human C1q as well as in their efficacy in mediating lysis of human erythrocytes in the presence of human complement. A major conclusion to emerge is that whereas IgG3 bound C1q better than did IgG1, the chimeric IgG1 was much more effective than all the other IgG subclasses in complement-dependent hemolysis. The IgG1 antibody was also the most effective in mediating antibody-dependent cell-mediated cytotoxicity using both human effector and human target cells. These results suggest that IgG1 might be the favoured IgG subclass for therapeutic applications.
Animals↗
Immunogenicity and antigenicity of immunoglobulins: detection of human immunoglobulin light-chain carbohydrate, using concanavalin A.
Concanavalin A binding to glycoprotein bands on nitrocellulose blots was used to detect mannose, sorbose, N-acetylgalactosamine and/or glucose residues on 100% (31/31) of human Bence Jones protein light chains, following sodium dodecyl sulphate-polyacrylamide gel electrophoresis. All (20/20) light chains form IgG myeloma proteins and light chains from a preparation of normal polyclonal human IgG were also bound by concanavalin A. The specificity of concanavalin A for glycoproteins was demonstrated by its binding to human Fc fragments and a human monoclonal anti-Rhesus D antibody (REG-A), but not to human albumin pFc' fragments and aglycosylated REG-A derived from cells grown in the presence of the glycosylation inhibitor tunicamycin. These results suggest that all Bence Jones proteins and light chains from myeloma IgG proteins contain mono- or oligosaccharides linked O-glycosidically to serine or threonine residues.
Acetylgalactosamine↗
Antagonism of interferon induction in spleen and adherent peritoneal cells of mice by the lipophilic antiviral muramyl peptide MTP-PE.
The immunomodulator muramyl tripeptide-phosphatidylethanolamine (MTP-PE) has been shown to enhance host resistance against a variety of experimental infections and to cure influenza virus infection in mice when given in a single dose, even at a late stage of the disease. Tests of its capacity to induce alpha/beta- and gamma-interferon (IFN-alpha/beta and -gamma) in vitro demonstrated that it is neither an inducer nor a primer of IFN synthesis. On the contrary, we found that it inhibits the induction of IFN-alpha/beta and -gamma by poly(rI:rC), Newcastle disease virus, lipopolysaccharide, or concanavalin A in adherent cells from the peritoneal cavity and spleen of mice. The antiviral activity of already induced or exogenously added murine IFN was, however, not impaired.
Acetylmuramyl-Alanyl-Isoglutamine↗
Immunogenic and antigenic epitopes of immunoglobulins. XIV. Antigenic variants of IgG4 proteins revealed with monoclonal antibodies.
Two IgG4 paraproteins having heavy chains of normal molecular weight are shown to be antigenically distinct in their reactivity profiles with 18 monoclonal antibodies having specificity for the IgG2 or IgG4 subclasses. One protein expresses IgG2 and IgG4 epitopes within the C gamma 2 domain. A second protein is deficient in the expression of IgG4 Fc-specific epitopes. These proteins will be of value in defining the structural basis of Fc effector functions and individual epitope expression.
Antibodies, Monoclonal↗
Immunogenic and antigenic epitopes of immunoglobulins. XVIII. Subpopulations of human lambda chains defined with a panel of monoclonal antibodies.
Following immunization with various lambda Bence-Jones proteins, over 100 hybridomas were established. A majority of the monoclonal antibodies (McAb) produced were demonstrated to recognize epitopes common to all lambda chains or unique to the immunogen. Twenty-nine McAb exhibited profiles of 'restricted' reactivity. Analysis with a panel of serologically defined antigens allowed McAb recognizing the lambda II subgroup to be identified. Other McAb recognized epitopes selectively expressed by lambda II and lambda III subgroup proteins. A further twenty-one McAb exhibited individual specificity profiles, some of which detect minor lambda chain subpopulations. Several of these McAb have potential for analysis of the clonality of specific antibody responses and for detecting monoclonal B-cell proliferations.
Antibodies, Monoclonal↗
Restricted light chain subgroup expression on human rheumatoid factor paraproteins determined by monoclonal antibodies.
Two hybridoma antibodies specific for determinants on the V kappa light chain subgroup have been produced and characterized. Antibodies C7 and B12 reacted with distinct V kappa epitopes irrespective of association with heavy chain class or subclass. Epitopes recognized by C7 and B12 were expressed on the light chain of IgG, IgA, and IgM and Bence-Jones paraproteins from the V kappa subgroup. However, a preferential association of both epitopes with IgM RF paraproteins was demonstrated. Hybridomas C7 and B12 reacted with 12/12 and 10/12 IgM RF paraproteins, respectively, but only with 3/6 IgM paraproteins, with no RF activity. Both epitopes C7 and B12, were immunodominant and conformation dependent, being detected by HA, HAI and ELISA on intact light chain but not isolated VK.
Animals↗
Evaluation of monoclonal antibodies having specificity for human IgG sub-classes: results of an IUIS/WHO collaborative study.
Seventy-four monoclonal antibodies (McAb) of putative specificity for human IgG (11), the IgG sub-classes (59) or Gm allotypes (4) have been evaluated for reactivity and specificity in eight laboratories employing different assay techniques or protocols. For the IgG, IgG3, IgG4, G1m(f) and G3m(u) specificities McAb have been produced that can be satisfactorily applied in most methodologies employed and have potential as reference reagents. The IgG1 and particularly IgG2 specificities proved problematical with all McAb evaluated demonstrating apparent assay restriction and whilst performing well in some assays proved to be poor or inactive reagents in others. However, the study identifies McAb individually suited to application within most commonly employed methodologies. Epitope display is the probable variability rather than capricious behaviour by the McAb. IgG1 and IgG2 were the least immunogenic of the sub-class proteins and there is evidence that epitope display is influenced by the physical and chemical procedures used to immobilize or fix antigen - a common requirement in the assay systems studied.
Antibodies, Monoclonal↗
Mortality discussions with case reports--cancer.
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Humans↗
Evidence that the platelet retention factor is separate from the factor VIII-related antigen and factor VIII.
Plasmas from a pregnant patient with von Willebrand's disease and from a patient with von Willebrand's disease who is taking Premarin had elevated levels of Factor VIII-related antigen and Factor VIII activity without any improvement in their platelet retention abnormality. When these were added to the blood from nonpregnant patients with von Willebrand's disease no significant improvement in platelet retention followed. This suggests that the "retention factor" is independent of the antigenic Factor VIII-like material.
Blood Coagulation↗