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F Emmrich

Publications and source records attributed to F Emmrich.

At least 145 records · Page 8Linked to original sources
PubMed1987

[Perspectives in the use of monoclonal antibodies in the therapy of neoplastic diseases].

In order to improve the efficiency of monoclonal antibodies against tumor-associated antigens, conjugates with toxins, cytostatics or radionuclides have been tested. Furthermore, antibody genes or gene segments can be altered or exchanged to reach enhanced specificity or novel biological functions of immunoglobulin molecules. In addition, monoclonal antibodies have been used recently for the direction, stimulation and activation of T lymphocytes, which are able to generate cytolytic potential against tumor cells. In this study we demonstrate selective activation and expansion of T-cell subpopulations by cross-linking the T-cell receptor complex with other differentiation antigens.

Antibodies, Monoclonal↗
PubMed1987

Idiotypic vaccinations: consideration towards a practical application.

We review the theoretical background as well as the available experimental data in animals and man on the possible use of anti-idiotypic antibodies as vaccines for the prevention of infectious diseases. In the first part, the basic experiments and concepts that fostered the idea of idiotypic vaccination are discussed. Although many basic aspects are still unknown, we conclude that the immune system can take antibody variable domains as representatives ("semiotypes") of foreign antigens not only in special cases, but also in a general sense. Among the major areas to be studied further are the events that regulate response to antibody in relation to those that regulate responses to antigen. Initial experiments suggest that responses to antibody may be directed intentionally towards a desired outcome. In the second part, we evaluate the actual medical need for idiotypic vaccination. We conclude that most novel vaccination regimes are likely to be developed with the help of protein chemistry and gene technology. Idiotypic vaccines may become applicable only in special, well-defined situations, such as cases of nonresponsiveness to antigen or cases of severe dysregulation of immunity by the antigen. The third part of the article deals with experimental models for idiotypic vaccination. A number of groups have performed protection experiments in various model infections of experimental animals using anti-idiotypic antibodies as vaccines. In a fair number of cases, involving infections with viral, bacterial, and parasitic microorganisms, protection has been successfully induced. In the fourth part, we summarize studies on idiotype expression in human antigen-driven immune responses. The limited data available suggest that human idiotype expression follows similar rules as in experimental animals. In particular, widely cross-relative idiotopes are readily detected using monoclonal anti-idiotopes. Antibodies to such idiotopes reacted with major proportions of the antibodies of a given specificity. Taken together, many factors point towards the feasibility of idiotypic vaccination.

Animals↗
PubMed1986

A recombinant 64 kilodalton protein of Mycobacterium bovis bacillus Calmette-Guerin specifically stimulates human T4 clones reactive to mycobacterial antigens.

A recombinant 64 kD protein of Mycobacterium bovis bacillus Calmette-Guerin (BCG) (antigen A), which amounted to approximately 2% of an E. coli lysate, was tested for its capacity to stimulate human T4 clones reactive to mycobacterial proteins. Two out of four crossreactive clones, established from a patient with tuberculoid leprosy, which could be stimulated by protein preparations of M. leprae and M. tuberculosis, and by particulate M. bovis BCG were also reactive to antigen A without further enrichment from E. coli lysate. In addition, BCG-reactive T cell clones from two of three healthy PPD+ donors reacted with antigen A. This finding shows that human T cell clones may be useful for probing gene-cloned proteins of potential value for vaccination against diseases where protection is mediated exclusively by T cells.

Clone Cells↗
PubMed1986

Isotype restriction of idiotopes associated with human anti-streptococcal A carbohydrate antibodies.

Sharing of idiotopes between IgG and IgM antibodies has been described with antibodies of various specificities in the literature. However, this does not seem to be the rule for human IgG and IgM antibodies with specificity to streptococcal A carbohydrate. Six idiotopes were described which are associated either with IgM or with IgG antibodies to one of the two major epitopes of streptococcal A carbohydrate: N-acetyl-D-glucosamine or alpha(1,2), alpha(1,3)-linked rhamnose oligomers. Some of the idiotopes are widely cross-reactive with antibodies of the corresponding specificity in other individuals. They were constantly found to be restricted to either IgM or IgG in all individuals tested so far. We discuss several alternatives to explain this finding and conclude that switching from IgM to IgG is either a very rare event in human B cells of this specificity, or leads to loss and gain of idiotopes and/or specificity due to frequent somatic mutations. The phenomenon of idiotope restriction to certain isotypes might be important if anti-idiotopic monoclonal antibodies are considered for use in therapeutical approaches aimed at the manipulation of antibody production.

Acetylglucosamine↗
PubMed1986

Synergism in the activation of human CD8 T cells by cross-linking the T-cell receptor complex with the CD8 differentiation antigen.

Resting human T cells can be activated and induced to proliferate by cross-linking the T-cell receptor complex (Ti/CD3) with anti-CD3 (T3) antibodies, such as OKT3, together with interleukin 2. Here we describe functional properties of another monoclonal anti-CD3 antibody (BMA 030) that, cross-linked in various ways, only weakly stimulates accessory-cell-depleted T-cell cultures. However, when cross-linked to anti-CD4 or anti-CD8 antibodies a markedly enhanced proliferation of the corresponding subpopulation is observed. We have concentrated on the analysis of CD8 cells and have found that BMA 030, when cross-linked together with anti-CD8 (T811), induced proliferation more than 100-fold greater than BMA 030 alone, whereas cross-linking with antibodies to other T-cell membrane antigens (HLA-A, B, or CD5) provided no or marginal synergistic signals. There was no synergistic effect when only one of the two antibodies, BMA 030 or T811, was cross-linked and the other was applied in soluble form. In contrast, each of the two antibodies alone, when applied in soluble form, inhibited activation induced by the cross-linked antibodies. The T-cell differentiation antigen CD8 has been implicated in the major histocompatibility complex (MHC) class I restricted specificity of CD8 T cells. In previous work from other laboratories only the negative influences of soluble anti-CD8 antibodies have been noted. In contrast, our results suggest that cross-linking between Ti/CD3 and CD8 may be a critical event in the activation of mature CD8 cells. We hypothesize that, in antigen-induced T-cell activation, CD8 and Ti/CD3 become cross-linked by their simultaneous binding to class I-associated structures. Such a mechanism, if required for proliferation in early T-cell ontogeny, could generate a selective pressure for CD8 cells to recognize class I-associated antigens.

Animals↗
PubMed1986

Human T-cell clones with reactivity to Mycobacterium leprae as tools for the characterization of potential vaccines against leprosy.

T-cell clones with the T4 phenotype were established from patients with tuberculoid leprosy. The antigen reactivity of these clones ranged from stringent specificity for Mycobacterium leprae to broad cross-reactivity with other mycobacteria. Killed M. leprae had a weak stimulatory capacity which could be enhanced by ultrasonication. Among the three candidate antileprosy vaccines, M. leprae, M. bovis BCG, and the ICRC (Indian Cancer Research Center) strain, the last was superior in stimulating cross-reactive T4 clones. This finding argues for a differential masking of similar or identical membrane antigens in various mycobacterial species. T-cell clones with defined reactivity patterns for mycobacterial antigens could be helpful tools for the characterization of an antileprosy vaccine.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1986

Human macrophage maturation and heterogeneity: analysis with a newly generated set of monoclonal antibodies to differentiation antigens.

We have analyzed the expression of late differentiation antigens during terminal in vitro maturation of human macrophages (M phi) from blood monocytes (MO) in comparison to their distribution among mature M phi residing in various tissue sites. By immunizing mice with M phi derived from blood MO by culture on hydrophobic Teflon foils, monoclonal antibodies (mAbs) were developed (MAX.1, MAX.2, MAX.3, MAX.11) that reacted with lineage-restricted differentiation antigens. These antigens were expressed exclusively on M phi or were markedly increased after in vitro differentiation. The only overlap to another hemopoietic cell lineage was observed with MAX.3, which is shared by platelets and megakaryocytes. In the course of M phi maturation in vitro, the MAX.1 and MAX.3 antigens are detected within the cytoplasm two days before they appear on the cell surface. In contrast, the MAX.11 antigen is expressed simultaneously in the cytoplasm and at the cell surface, is found in varying degrees on a minor portion of blood MO and U937 cells, and is expressed rapidly at high density during early M phi differentiation in vitro. Among conventional mAbs that do not react with MO we found those against the transferrin (TF)-receptor, the BA-2, and the PCA1 antigen to label M phi. M phi matured in vivo and isolated from body fluids were positive with some but not all MAX mAbs. Distinctive patterns were observed with pulmonary M phi, exudate M phi from pleural and peritoneal effusions, synovial fluids, and early lactation milk. M phi from the alveolar space, for example, constantly expressed the MAX.2 antigen but not the MAX.3 antigen. Pleural effusion M phi, however, did not react with the MAX.1 mAb, but in most cases, it did react with the MAX.3 mAb. The detection of novel differentiation antigens, all expressed on monocyte-derived M phi but differently expressed on site-specific M phi in situ, underlines the remarkable heterogeneity among human M phi. The expression of these antigens is flexible because those MAX antigens that were not expressed in situ could be induced if cells from distinct tissue sites were cultured in vitro for several days. MAX mAbs may be of potential value to study both the sequential stages of maturation within the M phi lineage as well as differential developments induced by various culture conditions in parallel to environmental factors in vivo.

Animals↗
PubMed1985

Human immune response to group A streptococcal carbohydrate (A-CHO). I. Quantitative and qualitative analysis of the A-CHO-specific B cell population responding in vitro to polyclonal and specific activation.

The immune response to the group-specific carbohydrate of group A streptococci (A-CHO) provides an informative in vitro model for the investigation of several aspects of human anticarbohydrate immune responses. A-CHO-specific B cells can be polyclonally activated by pokeweed mitogen (PWM), and, specifically, by in vitro immunization with streptococcal vaccine. High levels of A-CHO-specific antibodies, mainly directed to the immunodominant side chain N-acetyl-D-glucosamine (GlcNAc), occur in healthy adult individuals. Serum antibody levels are reflected in high frequencies of precursor B cells among peripheral blood lymphocytes. In one particular case, greater than 15% of all B cells activated by PWM for IgM production were found to produce IgM anti-A-CHO antibodies, as determined in limiting dilution experiments, as well as by analyzing Ig concentrations in bulk culture experiments. The case with the lowest proportion observed had 0.3% A-CHO-specific B cells among IgM-producing B cells. Preferential PWM activation of anti-A-CHO-producing B cells could be excluded. The comparison of the proportions of anti-A-CHO IgM produced in vivo, and of B cells producing antibodies of this specificity in peripheral blood, suggests a similar distribution of specific precursor B cells in the antibody-producing lymphoid tissue compartments and in peripheral blood. However, nearly all specific antibodies produced in vitro belong to the IgM isotype, whereas IgG anti-A-CHO in high amounts, mostly exceeding the specific IgM, was found only among anti-A-CHO antibodies produced in vivo. Low anti-A-CHO IgG production was seen in polyclonally activated as well as in antigen-activated cultures, whereas, in contrast, total IgG was produced in considerable amounts after polyclonal activation. This suggests a different distribution pattern, and/or diverse differentiation requirements for anti-A-CHO-producing B cells, compared with other B cell species.

Adult↗
PubMed1985

Monoclonal antibodies against differentiation antigens on human macrophages.

Human macrophages matured in vitro from blood monocytes without additional exogenous activation were used to produce monoclonal antibodies (mAbs). Ten of them were selected for high avidity and the best discrimination between mature macrophages and a panel of other cells including freshly prepared monocytes, B cells, T cells, granulocytes and thrombocytes. Five mAbs (MAX. 1, MAX. 2, MAX. 3, MAX. 11, MAX. 24) were found to detect macrophage differentiation antigens. One mAb (MAX. 26) detects an antigen which is shared by mature macrophages and T cells.

Animals↗
PubMed1985

Recombinant human interleukin 2 directly provides signals for the proliferation and functional maturation of murine B lymphocytes.

In this study the effect of recombinant human interleukin 2 (rec.hIL-2) on the proliferation and maturation of B lymphocytes was investigated. It was found that the presence of rec.hIL 2 results in proliferation of mitogen (LPS)-activated B cell blasts. In addition, it is shown that highly enriched murine B cells can be induced by rec.hIL-2 to proliferate and to develop into antibody-secreting cells (PFC) in the presence of antigen (SRBC). When tested for its effect on B cell preparations enriched for resting (small) or activated (blasted) B lymphocytes, it was found that rec.hIL 2 provides signals for both B cell populations to develop into PFC. In contrast, induction of proliferation by the same lymphokine source was only seen in blasted B cells. The data indicate that IL 2 is involved in the generation of B effector cells by directly acting on their precursors thereby providing differentiation as well as proliferation signals.

Animals↗
PubMed1985

Recombinant human interleukin 2 acts as a B cell growth and differentiation promoting factor.

Human B cells appropriately activated by a B cell mitogen are rendered susceptible to human Interleukin 2 (IL-2) as demonstrated with recombinant human IL-2 (rec. h IL-2). They show increased proliferation and drastically enhanced immunoglobulin secretion. Susceptibility to IL-2 is accompanied with the expression of the IL-2 receptor (Tac antigen) on B cells. The data suggest that IL-2 is one of the lymphokines directly involved in the activation of B lymphocytes.

B-Lymphocytes↗
PubMed1985

Two human IgM myeloma proteins with unusual specificities for streptococcal carbohydrate-associated epitopes.

Five hundred and fifty human sera from patients with IgM myeloma or Waldenström's macroglobulinaemia were screened by a solid-phase enzyme-linked immunoassay for binding to the carbohydrate of group A streptococci (A-CHO). Two of them (AC8 and AC179) contained immunoglobulin, which bound specifically to A-CHO even at serum dilutions of 1:10(7). Using synthetic oligosaccharides coupled to protein for inhibition studies, the fine specificities of AC8 and AC179 were determined. AC179 is directed to alpha-linked rhamnose oligosaccharides. AC8 appears to be specific for N-acetyl-D-glucosamine (GlcNAc) side chains beta(1----2)-linked to rhamnose, whereas GlcNAc side chains in A-CHO are reported to be beta(1----3)-linked to the rhamnose backbone. Naturally occurring anti-A-CHO antibodies consist mainly of low-affinity antibodies to such beta(1----3)-linked GlcNAc. In contrast, both myeloma antibodies show more than 10 times higher relative affinities to A-CHO than antibodies prepared from normal human serum (anti-GlcNAc and anti-A-CHO, respectively) by selection for high affinity in the elution procedure. AC179 induced complement activation in the presence of A-CHO.

Acetylglucosamine↗
PubMed1985

Idiotope mapping on the variable region of an antibody clonotype produced by normal (nonmalignant) human B cells.

Human anti-N-acetyl-D-glucosamine (GlcNAc) antibodies were prepared by affinity chromatography from serum of a healthy donor (MSS). They were heterogeneous but contained a unique antibody clonotype (1A) representing 7% of all anti-GlcNAc antibodies. Out of a series of monoclonal anti-idiotopic antibodies (anti-Id mAb), we identified five antibodies that bound to clonotype 1A as shown by isoelectric focusing and Western blotting. Two of them were specific for clonotype 1A (10F59 and 13F15), thus indicating its clonal origin. However, three anti-Id mAb (16F433, 16F539, and 16F812) bound to various additional portions of anti-GlcNAc antibodies of donor MSS. With the exception of one mAb, all anti-Id mAb have very similar relative affinities to clonotype 1A, so results from competition experiments between the different antibodies and between each antibody and antigen should reveal spatial relationships between the corresponding Id and between each Id and the antigen-combining site. The results show a consistent topography of Id on the V-region of clonotype 1A. Id 59, 812, and 433 were found to be arranged in one cluster (cluster I), whereas Id 15 and 539 belonged to a second cluster (cluster II). Cluster I resides completely in the antigen-combining site, whereas only Id 15 of cluster II weakly overlaps with the binding site. Our study demonstrates an analysis of spatial relationships of Id expressed on a human antibody clonotype. To our knowledge, this is the first demonstration of Id mapping on antibodies produced by a normal (nonmalignant) B cell clone that should be accessible to regulatory signals. Such analysis may contribute to a more detailed characterization of anti-Id mAb, and may provide additional information for a better understanding of their immunoregulatory effects.

Acetylgalactosamine↗
PubMed1984

Characterization of a major human antibody clonotype (1A) by monoclonal antibodies to combining site-associated idiotopes.

To identify major human antibody clonotypes with specificity to N-acetyl-D-glucosamine (GlcNAc), affinity-purified antibody preparations of different human individuals were analyzed by isoelectric focusing (IEF). A major clonotype (1A) was identified representing 7% of all anti-GlcNAc antibodies of one donor (no. 371). Anti-GlcNAc antibodies of donor 371 were used as immunogen to prepare monoclonal anti-idiotopic antibodies (mAb). Two anti-idiotopic mAb were specific for the major clonotype 1A, as shown by blotting of the anti-GlcNAc antibodies after IEF in thin-layer agarose to nitrocellulose filters and staining with either iodinated antigen or iodinated anti-idiotopic mAb. The two anti-idiotopic mAb 13F15 and 10F59 were further analyzed with respect to the antigenic determinant which they recognize. Both were directed to combining site-related determinants as shown by inhibition studies. Although 13F15 has a 500-fold higher binding capacity (relative affinity) equal amounts do not inhibit more than 50% of 10F59 binding, suggesting that the two mAb detect two closely related, but not identical, idiotopes in the antigen combining site of clone 1A. Although clonotype 1A is a unique antibody exclusively found in IEF of donor 371, the idiotope 1A.1, defined by mAb 13F15, is a recurrent determinant detectable on different anti-GlcNAc spectrotypes in various human sera.

Acetylglucosamine↗
PubMed1983

A cross-reacting human idiotype (B17) associated with antibodies to N-acetyl-D-glucosamine. Specificity, immunoglobulin class association, and distribution in the population.

This report describes the study of the expression of an idiotype in the human population which is associated with antibodies to N-acetyl-D-glucosamine (GlcNAc) present in most human sera presumably due to streptococcal infections. The idiotype is identified with antisera and monoclonal antibodies prepared against the IgM (kappa) antibody secreted by the Epstein-Barr virus-transformed human B cell line B17. At least 90% of 207 individuals tested had immunoglobulin with B17 idiotypic determinants in their sera, as demonstrated with conventional and one monoclonal anti-idiotypic antibody. Another monoclonal anti-idiotypic antibody reacted with antibodies in only a few of the sera. No correlation was found between the level of expression of different idiotopes in individual human sera, suggesting molecular heterogeneity of the B17-positive antibody population. B17-positive immunoglobulins are to a large extent specific for GlcNAc but represent only a minor population of all GlcNAc-specific antibodies in human sera. B17 determinants are on IgM (kappa) in all human sera and on IgG and IgA in some. In addition, some lambda-bearing Ig was found to react with anti-B17 antisera, suggesting the detection of VH-associated idiotypic determinants in this experimental system.

Acetylglucosamine↗
PubMed1980

[Comparative studies of the specificity of idiotypic guinea pig and carp antisera].

The specificity of guinea-pig- and carp-anti-idiotypic antisera were compared by using the radioimmunoassay and the passive hemagglutination inhibition test. Guinea-pigs and carps were immunized with the IgA/k mouse myeloma protein S117 which has binding activity to the hapten N-acetylglucosamine. the resulting antisera were idiotypically specified by absorption and the activity was determined by the binding of the radiolabeled idiotype S117. The binding curves of guinea pig and carp anti-idiotypic antisera are very similar. The idiotype-anti-idiotype reaction could be partially inhibited by the specific hapten N-acetylglucosamine but not by N-acetylgalactosamine. Both antisera, guinea pig and carp, respectively, are different in respect to the immunoglobulin class of anti-idiotypic antibodies which react with the idiotype S117. In the case of the guinea pig antisera the anti-idiotypic antibodies are mainly of the IgG-type whereas the anti-idiotypic antibodies of carp are exclusively of IgM-type. This important difference is discussed.

Animals↗