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K Blaser

Publications and source records attributed to K Blaser.

At least 181 records · Page 10Linked to original sources
PubMed1987

Two monoclonal antibodies that discriminate between allelic variants of human low density lipoprotein.

Human low density lipoprotein shows a genetic polymorphism, the so-called Ag-system. it consists of 5 pairs of allelic epitopes, x/y, al/d, c/g, t/z, and h/i, which are localized on apolipoprotein B. We have generated a large number of monoclonal antibodies against low density lipoprotein. Two of them, D2E1 and H11G3, recognize epitopes related to this genetic polymorphism. Direct ELISA and ELISA inhibition experiments with different low density lipoproteins of known phenotype showed that D2E1 is directed against the allelic epitope c and H11G3 against d. The two antibodies were used for the characterization of low density lipoprotein in sera from different blood donors and the results compared to those obtained by passive hemagglutination using human allotypic anti-sera. Sera from homo- or heterozygous donors (which display the relevant epitope) could be distinguished from the sera of homozygous donors (which lack the epitope) with the monoclonal antibodies described.

Alleles↗
PubMed1987

Age-dependent changes in isotype expression and down-regulation of C57BL/6 mice.

Age-related changes in antibody response and tolerance inducibility are polymorphic; in this paper isotype changes in ageing C57BL/6 mice are examined. Female C57BL/6 mice of various ages were immunized with either heat-aggregated RGG (a-RGG) or phosphorylcholine conjugate of RGG (PC-RGG); other animals of the same ages were given aggregate free RGG, followed by injections with either aggregated RGG or haptenated RGG. Sera from these four groups were analysed for antibody isotype. The data presented here indicate that age-related changes in isotype predominance and magnitude are different for different determinants. The capacity to be down-regulated appeared to undergo different age-related changes with different isotypes: there is split tolerance in isotypes. Age-dependent changes in T- and B-cell tolerance could be deduced by comparing responses of animals to hapten and to carrier determinants. In 5-week-old animals tolerance to hapten was more profound than tolerance to carrier. It was concluded that T-cell regulation dominated the response at this age. With advancing age, i.e. by 95 weeks, tolerance is observed in response to hapten but not in response to carrier determinants. We concluded that suppressor cells were induced by aggregate free RGG and affected the response of 'naive' but not of 'experienced' B cells.

Aging↗
PubMed1987

The IgE antibody response to the phosphorylcholine hapten.

The immune response to the phosphorylcholine (PC) hapten elicited by PC-keyhole limpet hemocyanin (KLH) is composed of 2 groups of antibodies with specificity to either PC or phenylphosphorylcholine which were designated as group I and II anti-PC antibodies, respectively. We demonstrate that anti-PC IgE antibody expression is restricted to group II antibodies and does not display the T15 idiotype. Accordingly anti-PC IgE antibodies recognize the same epitope (PC-phenyl) as IgG1, IgG2a and IgG2b antibodies which is different from that (PC) recognized by IgM and IgG3 antibodies. A monoclonal anti-PC IgE antibody, representing group II characteristics was established. From amino acid sequences of light chains of purified group I and II antibodies from serum as well as of monoclonal representatives thereof it appears that both populations are relatively homogenous and represent independent clonal expressions. Nevertheless the formation of anti-PC IgE antibodies in mice can be suppressed by isologous anti-T15 anti-idiotypic antiserum. This antiserum, however, crossreacts with different anti-PC antibodies including monoclonal group II anti-PC IgE antibodies and is composed of a large number of anti-idiotopes. An analyses performed with monoclonal anti-T15 idiotopes demonstrates that some but not all antibodies suppress the formation of anti-PC IgE. We conclude that syngeneically induced anti-idiotypic interactions may display regulation of a wide range of specificities affecting responses to various antigenic determinants.

Antibody Formation↗
PubMed1986

Production and characterization of monoclonal antibodies against human neuroblastoma.

MAb were derived from mice immunized with cells of the human neuroblastoma line IMR-32. Five hybridomas were selected according to their selective binding to human cell lines, tumors and normal tissues. One of them, CE7, reacted with all sympatho-adrenomedullary cells (neuroblastoma, ganglioneuroblastoma, ganglioneuroma, pheochromocytoma, adrenal medulla, sympathetic ganglion cells). Weak cross-reactivities were observed with melanocytes and with some human melanoma and glioma cell lines. The antigen recognized by CE7 was markedly expressed on neuroblastoma tumors of all histological grades, independently of the adrenergic or cholinergic nature of these cells. MAb derived from clones AD2, BC1, BC4 and CB10 bound variably to some, but not to all, neuroblastoma cells. By using these MAb, 3 phenotypes of neuroblastoma lines could be distinguished. The binding profiles of these types, however, showed no correlation with origin of the cell lines or stage of the disease.

Animals↗
PubMed1986

Age- and strain-dependent polymorphism in IgE antibody against the phosphorylcholine hapten.

The magnitude of the IgE antibody response against the phosphorylcholine (PC) hapten and the rate of age-related change of IgE formation is polymorphic in the three long-lived and six relatively short-lived strains of mice studied. Long-lived mice showed an early increase, followed by a decline in the levels of anti-PC IgE antibody. The rate of increase and decrease was strain dependent. Among short-lived strains, MRL/Mp-lpr and MRL/Mp-+ mice showed an early decline in IgE antibody. The extent and rate of decline with age was more rapid in MRL/Mp-lpr animals than in MRL/Mp-+ mice. In contrast, there was an early increase of IgE antibody in female SJL, NZB/BIN, BXSB/Mp and male BXSB/Mp. Thus, opposite age-related changes in IgE antibody production can occur in animals with a tendency to develop autoimmune disease. In hybrids of (SJL X BALB/c)F1 and (BALB/c X MRL/Mp-lpr)F1, the levels of IgE antibodies were higher than those observed in either parental strain, and declined steeply with advancing age. We suggest that this could be attributed to recessive inheritance.

Aging↗
PubMed1986

Fine specificity and idiotype expression of anti-phosphorylcholine IgE and IgG antibodies.

The immune response to the phosphorylcholine (PC) hapten elicited in BALB/c mice by PC-keyhole limpet hemocyanin (KLH) is composed of 2 groups of antibodies with specificity to PC and phenyl-PC, respectively. They were designated as group I and group II anti-PC antibodies. In this report we demonstrate that anti-PC IgE antibodies elicited by PC-KLH or PC-ovalbumin belong to the group II and do not express the T15 idiotype. Anti-PC IgG1, IgG2a and IgG2b antibodies express group I characteristics in the primary response and bear the T15 idiotype. Later, after 5 weeks and 3 injections of PC-KLH or PC-ovalbumin, a change in these isotypes to group II antibodies is observed. In contrast, anti-PC IgE is a group II antibody throughout progression of the immune response. The regulation of group I and group II antibody expression in serum is independent of the genetic background of the animals.

Animals↗
PubMed1986

Suppression of the anti-hapten IgE antibody response with hapten-modified spleen cells.

Spleen cells of BALB/c mice were chemically modified with phosphorylcholine or benzylpenicilloyl hapten. The i.v. administration of such cells into syngeneic animals suppressed the formation of specific IgE antibodies against the respective hapten. The IgE antibody response against ovalbumin, which was used as an immunogenic carrier for the haptens, was not affected and the anti-hapten IgG or IgG1 response remained at the levels of the controls. The suppression could be transferred into X-irradiated mice by T cells from tolerized animals. Moreover, it was demonstrated that not only the induction of IgE, but also an established anti-hapten IgE antibody response is accessible to suppression by treatment with hapten-modified spleen cells from syngeneic animals. The results indicate that the i.v. administration of antigen coupled to syngeneic spleen cells induces T cells which suppress the formation of specific IgE antibodies in the primary and the secondary response without significantly affecting the formation of IgG antibodies.

Animals↗
PubMed1986

Isotype-specific resistance against tolerance induction in SJL mice.

Age-related changes in antibody response of SJL mice were examined in terms of isotype expression after treatment with immunogen or with immunogen, preceded by the molecule in normally tolerogenic form. We report here that tolerance induction and resistance to down regulation are isotype specific. Tolerance can be induced in terms of all detectable isotypes at the age of 5 weeks. In older SJL mice, tolerance to the carrier is found in IgM antibody, whereas there is resistance against down regulation in terms of IgG2a and IgG2b isotypes, and sensitization in terms of IgG3, IgG1, and IgA antibody. Furthermore, the degree of down regulation is determinant dependent. This was observed when older SJL mice, pretreated with the carrier in a normally tolerogenic form, were immunized with haptenated carrier and tested for their response to hapten and carrier determinants. In this case, IgA antibody shows tolerance to the hapten and sensitization by carrier determinants.

Animals↗
PubMed1986

Suppression of established IgE antibody responses with isologous anti-idiotypic antibodies in guinea pigs.

Guinea pigs of strains 2 and 13 can produce isologous anti-idiotypic (aIds) antibodies against anti-benzylpenicilloyl (anti-BPO) IgG, following immunization with affinity-purified anti-BPO antibodies of the same strain. The specificity of aId was determined by inhibition of binding of aId to Fab(t) in ELISA. The results showed that the reaction of strain 2 (anti-BPO)aId can be inhibited with syngeneic anti-BPO Fab(t) and to a smaller degree with anti-BPO Fab(t) of strain 13. On the other hand, strain 13 (anti-BPO)aId reacted exclusively with syngeneic anti-BPO Fab(t). In both cases, binding of aId to anti-BPO Fab(t) could not be inhibited with BPO-epsilon-aminocaproic acid, indicating that these aId are not directed against the antigen-combining site. The effect of isologous aId on both short- and long-time established IgE responses was studied in guinea pigs of strain 13. In both situations, administration of isologous aId resulted in suppression of the anti-BPO IgE antibody response. The suppressive effect was antigen-specific and lasted for several weeks: in the case of an early-response IgE remained suppressed despite additional booster injections of antigen. In contrast to the IgE response, the production of anti-BPO IgG antibodies was only slightly affected.

Animals↗
PubMed1985

Immune response, tolerance circumvention and autoantibodies in aging MRL/Mp-lpr and MRL/Mp-+ mice.

Isotype distribution was analyzed, as a function of age in MRL/Mp-lpr and MRL/Mp-+ mice. The mice were tested for: (1) "spontaneous" response to nucleic acid (2) induced response to alum-precipitated phosphorylcholine-rabbit gamma globulin (PC-RGG) (immunized animals) and (3) induced response to alum-precipitated PC-RGG after pretreatment with aggregate-free RGG (tolerized-immunized animals). "spontaneous" nucleic acid antibodies of isotypes, other than IgM, increased as animals became older. The quantity of RGG antibody declined as a function of the age at which animals were immunized. Young tolerized-immunized animals made less antibody of all isotypes than did immunized animals. In later life, resistance against tolerance induction developed. Aggregate-free RGG sensitized older animals and, thus, augmented the response to alum-precipitated PC-RGG. Up to the age of 20 weeks, spontaneous antibody and antibody of tolerized-immunized animals showed striking similarities in age- and strain-dependent changes of IgG2b and IgA isotypes. Results were discussed in terms of: (1) a defect in down regulation of immune responsiveness, which contributes to the initiation of autoimmunity and age-dependent resistance to tolerance induction; (2) regulatory mechanisms for isotype switching, which contribute to resistance to tolerance induction, whether naturally occurring or experimentally induced; and (3) age-related immunological changes which are inherent in the MRL/Mp genome, the mutant gene, lpr/lpr, accelerating the changes.

Aging↗
PubMed1985

Non-specific binding of mouse IgM antibodies to lipid antigens.

Galactocerebroside (GC) is a major component expressed on the surface of oligodendrocytes and Schwann cells. It plays a role in neuronal-glial interaction that results in myelinization. In this paper we describe a method to estimate anti-GC antibodies by ELISA. Furthermore we found that IgM antibodies of mice immunized with GC-unrelated antigens, and which are not specific for GC, bind in a non-specific way to this compound. Thus only assays which avoid the detection of IgM antibody can be used to estimate anti-GC antibodies. Moreover, we showed that serum of immunized mice bind also non-specifically to brain cells of newborn mice.

Animals↗
PubMed1985

Isotypic and idiotypic characterization of anti-bee venom phospholipase A2 antibodies.

It was shown that anti-bee venom phospholipase A2 antibodies (anti-PLA) of bee keepers belong mainly to the IgG4 class. Furthermore anti-PLA of different individuals are idiotypically related to each other. This was shown by the binding of heterologous antiidiotypic antibodies, produced against anti-PLA IgG from single donors, to anti-PLA F(ab')2 of different individuals. Therefore, the anti-PLA response provides a human model to study the idiotypic regulation of isotypes in a defined system.

Antibodies↗
PubMed1984

Regulatory effects of isologous anti-idiotypic antibodies on the formation of different immunoglobulin classes in the immune response to phosphorylcholine in BALB/c mice.

BALB/c mice were immunized with purified phosphorylcholine (PC)-specific myeloma protein of the TEPC-15 tumor, which bears the major idiotype of the anti-PC response (T15 Id) in this mouse strain. Four months after establishing the anti-idiotypic response, animals were immunized with PC-keyhole limpet hemocyanin under conditions which normally lead to IgE antibody formation. The expression of anti-PC antibodies of each immunoglobulin class was compared to a group of matched control mice not immunized with T15. In BALB/c mice producing anti-idiotypic antibodies the formation of anti-PC IgM, IgG1, IgG2, IgG3 and IgE was suppressed to various extents and for different lengths of time. An exception to this observation was the formation of anti-PC IgA antibodies, in that no significant difference was measured between the two groups of mice. BALB/c mice immunized in the same way with the PC-specific myeloma proteins of the MOPC-167, MOPC-511 and MOPC-603 tumors produced normal levels of anti-PC IgE and IgG antibodies. These results suggest that T15 idiotype-positive antibodies are probably formed within all classes of specific antibodies expressed during an immune response to PC. The possibility of extending the phenomena of anti-idiotype-induced suppression to the level of various classes of specific antibodies, including IgE, might be of interest in the treatment of some allergic diseases.

Animals↗
PubMed1984

Production and characterization of monoclonal antibodies to the myelin glycolipid sulfatide.

Sulfatide is enriched in the myelin sheath and accounts for 5% of the total lipids in this membrane. In the present work we describe the production and characterization of mouse monoclonal antibodies against sulfatide. The antibodies were detected and characterized in a previously described ELISA test system. The clone AIC3IA2 produced antibodies of the IgG3 class with high specificity for sulfatide. These antibodies showed almost no cross-reactivity with galactocerebroside or with any of the other lipids we tested. When used with the peroxidase antiperoxidase technique the antibodies stained a cell population either in fixed or unfixed brain cell cultures, indicating a surface localization of sulfatide in the respective cell population. In double-staining experiments the stained cell population was identified as myelin basic protein-positive oligodendrocytes.

Animals↗
PubMed1983

Production and characterization of mouse antibodies against the brain lipid sulfatide.

One of the lipids in the myelin sheet is sulfatide, a galactosphingolipid. Our aim was to develop a test system to detect and characterize antibody against this lipid. Mouse anti-sulfatide antibody was estimated by a solid-phase microtube assay with labeled Staphylococcus aureus protein A. With labeled rabbit anti-mouse Ig antibody, there was no difference between mouse anti-sulfatide serum and control sera from animals immunized with unrelated antigens. Results show that BALB/c mice produce antibodies against sulfatide if this low molecular weight compound is injected together with cholesterol, lecithin and bovine serum albumin. The antisera are specific for sulfatide but crossreact with galactocerebroside. However, mouse IgM antibody binds to sulfatide-coated polyvinyl plates non-specifically. Thus, only test procedures which avoid detection of IgM antibody can be used to estimate antibody specific for sulfatide and probably also for other lipophilic compounds.

Animals↗