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Biomedical subjects

K Blaser

Publications and source records attributed to K Blaser.

At least 199 records · Page 11Linked to original sources
PubMed1983

Effect of passively administered isologous anti-idiotypes directed against anti-carrier (ovalbumin) antibodies on the anti-hapten IgE and IgG antibody responses in BALB/c mice.

Recently we have shown that active immunization of syngenic animals with anti-ovalbumin antibodies evokes an anti-idiotypic (aId) response, which in consequence leads to suppression of the anti-hapten (benzylpenicilloyl, BPO; dinitrophenyl, DNP) IgE and IgG formation subsequently attempted by immunization with low doses of hapten-OVA conjugates. In this work we describe attempts to suppress a primary or an already established anti-hapten IgE response by passive administration of (anti-carrier) anti-idiotypes to BALB/c mice. Our results show that ongoing anti-BPO or anti-DNP IgE responses can be depressed by injection of (anti-ovalbumin) aId, provided mice were previously immunized with conjugates of the haptens with the ovalbumin (OVA) carrier. The same animals suppressed for IgE also produce less anti-hapten and anti-carrier IgG antibodies but only after 5-6 weeks following the aId injection. The primary IgE response could be blocked by treating mice with (anti-OVA) aId and antigen at the same time.

Animals↗
PubMed1981

[Effect of anti-idiotypes on the production of phosphorylcholine-specific antibodies].

BALB/c mice were immunized with purified phosphorylcholine (PC)-specific myeloma proteins of the TEPC-15 and M167 tumors. After the respective isologous anti-idiotypic responses had been established, and after an additional resting period of four months, animals were immunized with phosphorylcholine-hemocyanin in a procedure normally leading to formation of IgE in addition to antibodies of other classes. The experiment shows that BALB/c mice producing (T15) anti-idiotypes depress the formation of anti-PC IgE, IgM, IgA antibodies, while stimulatory effects on the IgG response are observed. This demonstrates that IgE bears idiotypes similar or identical, to antibodies of other classes, and that anti-PC-IgE antibodies mainly bear the T15 idiotype or idiotypes crossreacting with isologous anti-T15. On the other hand, cells responsible for regulation or production of antibodies of different classes show different susceptibility to regulation by anti-idiotypes. The formation of IgE antibodies seems to be particularly susceptible to suppression by anti-idiotypes, a fact which may lead to new treatments for some allergic diseases and to new insight into the mechanisms of hyposensitization therapy.

Animals↗
PubMed1981

Investigation of a syngeneic murine model for the study of IgE antibody regulation with isologous antiidiotypic antibodies.

A murine experimental model to study in vivo effects of antiidotypic antibodies (aId) on the benzylpenicilloyl- (BPO) ane phosphorylcholine- (PC) specific IgE and IgG responses has been investigated. Isologous aId against anti-BPO antibodies and against the PC-specific myeloma proteins T15 and M167 have been administered to BALB/c mice previously sensitized with (BPO) carrier protein or PC keyhole limpet hemocyanin. One single injection of aId caused depression of anti-BPO IgE antibody levels for 2-3 weeks, whereas the anticarrier protein IgE response had not been affected. Longterm depression of anti-Pc IgE was achieved when anti-T15 antiserum has been administered three time to PC keyhole limpet hemocyanin immunized mice. Suppression of anti-BPO IgE and IgG antibodies has been achieved for a long period in mice actively producing anti-BPO aId. These results show that different individuals of the BALB/c mouse strain share major idiotypic determinants in IgE and IgG antibodies and the IgE antibody formation is accessible to suppression by isologous aId. These findings permit to integrate IgE regulation into the basic concepts of autologous immune regulation and might finally lead to applications in the treatment of IgE-mediated allergic syndromes.

Animals↗
PubMed1981

Mouse myeloma proteins with lambda 2 and lambda 3 light chains.

Serum and ascites fluid from mice bearing 260 different myeloma tumors were screened serologically for myeloma proteins having light chains like that of L315, the lambda 2 chain produced by myeloma MOPC-315. Four proteins, made by myelomas TEPC-952, CBPC-49, ABPC-72, and SAPC-15, were identified. Their light chains were essentially indistinguishable serologically from L315, and each of them also yielded the characteristic C-terminal amino acid (leucine) and C-terminal tryptic peptide of L315. However, amino acid sequences and other findings reported elsewhere have revealed that although the light chain of TEPC-952 is indeed a lambda 2 chain, the light chains of the others (CBPC-49, ABPC-72, and SAPC-15) represent another, slightly different type of light chain, which has been designated lambda 3.

Amino Acids↗
PubMed1981

Suppression of anti-hapten IgE and IgG antibody responses by isologous anti-idiotypic antibodies against purified anti-carrier (ovalbumin) antibodies in BALB/c mice.

The studies described here show that BALB/c mice actively producing isologous anti-idiotypic antibodies (ald) after immunization with purified, syngeneic anti-OvA antibodies exhibit depressed anti-hapten and anti-carrier IgE and IgG antibody responses, provided that hapten-OVA conjugates are used to mount the immune responses. We suggest that carrier-specific helper T cells (CTh) for IgE and IgG antibody production carry idiotypes similar or identical to those among purified anti-OVA IgG antibodies. The mode of regulation of immune responses by anti-carrier-ald may be different from that exerted by anti-hapten-alD. Although anti-carrier-ald may block or deplete CTh and thereby prevent help for immunoglobulin production by B cells, anti-hapten-ald may induce T suppressor cells (Ts).

Animals↗
PubMed1980

Synthesis of carboxyl terminal segments of beta-subunit of human chorionic gonadotropin. Application of the two-phase method.

The synthesis in solution of carboxyl terminal peptide segments of the beta-subunit of human chorionic gonadotropin is described. The protected segments include sequences 119-131, 132-137, and 138-145. The syntheses were based on a standardized liquid-liquid extraction program for routine purification of intermediates (two-phase method). Condensation of terminally deblocked segments afforded protection peptides 132-145, 126-145, 120-145, and 119-145. Protected peptides 126-145 and 120-145 were deprotected in liquid hydrogen fluoride and used in conjugated form for immunization of rabbits. Data on the specificity of the antibody response are reported.

Amino Acid Sequence↗
PubMed1980

Liquid-liquid extraction in peptide synthesis.

An efficient procedure of peptide synthesis in solution based on liquid-liquid extraction for the purification of intermediates (two-phase method) is described. Generally, peptide segments of 10 and in favorable cases 15 amino acids can be prepared by using conventional blocking groups. Special blocking groups adapted for optimal performance are discussed. Simple equipment enabling rapid synthesis is also described.

Amino Acid Sequence↗
PubMed1980

Effect of epitope density on the induction of the IgE immune response in mice.

The effect of hapten density on benzylpenicilloyl (BPO)-protein conjugates upon the induction of BPO-specific IgE immune response was investigated in BALB/c and C3H mice. Bovine gamma-globulin (BGG) and ovalbumin (OA) were employed as carrier proteins. In both strains of mice, moderately substituted conjugates (BPO19-BGG, and BPO-OA with an epitope density from 2 to 7.5) elicited a persistent BPO-specific IgE, while heavily substituted conjugates (BPO38-BGG) induced only a transient response. In contrast, lightly substituted conjugates (BPO3.2-, BPO9.5-BGG, and BPO1-OA) failed to produce BPO-specific IgE antibodies. There was no significant difference in carrier-specific IgE immune response among these various conjugates. These results suggest that moderately substituted hapten-protein conjugates are one of the favorable conditions for eliciting hapten-specific IgE immune response in mice.

Animals↗
PubMed1980

Rat mast cell degranulation triggered by murine anti-idiotypic antibodies.

Triggering of rat mast cell degranulation by murine anti-idiotypic antibodies (anti-Id) was investigated, using rat passive cutaneous anaphylactic (PCA) reactions as the method of evaluation. It was shown that the interaction between isologous murine anti-Id directed against anti-benzylpenicilloyl (BPO) antibodies and BPO-specific IgE molecules on the cell surface can induce PCA reactions on rats. The mechanism of cell activation by anti-Id was briefly discussed.

Animals↗
PubMed1980

Suppression of the benzylpenicilloyl- (BPO) specific IgE formation with isologous anti-idiotypic antibodies in BALB/c mice.

In vivo effects of actively produced or passively administered isologous anti-idiotypic antisera (aId) on the benzylpenicilloyl- (BPO) specific IgE and IgG formation in BALB/c mice have been studied. Isologous anti-BPO aId were raised in BALB/c mice by immunization with purified anti-BPO antibodies isolated from ascites induced with BPO-bovine gamma-globulin in the same mouse strain. Mice producing isologous anti-BPO aId exhibited long-term suppression of BPO-specific IgE and IgG antibody responses induced by BPO-ovalbumin (BPO-OVA) in aluminum hydroxide. Simultaneously, they produced increased amounts of anti-BPO aId after each challenge with the BPO-OVA antigens. Passive administration of isologous anti-BPO aId into syngeneic mice previously sensitized with BPO-OVA caused depression of BPO-specific IgE antibody levels for 2 to 3 weeks. When anti-BPO IgE had again reached its previous level, passively administered aId had decreased to the level of untreated mice. Passive administration of anti-BPO aId also depressed the primary anti-BPO IgE formation for 2 to 3 weeks. In all these experiments the IgE antibody formation against the carrier proteins used for BPO-antigens was not affected. These results show that IgE and IgG antibodies share major idiotypic determinants and that IgE production is accessible to regulation by aId.

Animals↗
PubMed1979

Suppression of phosphorylcholine-specific IgE antibody formation in BALB/c mice by isologous anti-T 15 antiserum.

In order to study the regulation of IgE antibody formation, isologous anti-idiotypic antisera against the phosphoryl choline (PC)-specific BALB/c myeloma proteins T 15 and M 167 were passively administered to BALB/c in the course of an anti-PC IgE response. Isologous anti-T 15 antiserum had a long-lasting suppressive effect on the formation of IgE antibodies with PC specificity, whereas administration of anti-M 167 antiserum had no or only little effect, similar to that of normal BALB/c serum. This indicates that anti-PC IgE antibodies consist mainly of the T 15 idiotype or of cross-reacting idiotypes, and that IgE response is accessible to regulation with anti-idiotypic antibodies. This murine model may permit the study of regulation of an IgE response largely restricted to few defined idiotypes characterized as tumor proteins.

Animals↗
PubMed1978

Lambda2 light chains in normal mouse immunoglobulins.

Light (L) chains of the lambda type are rare in mouse immunoglobulins. One lambda chain, the L chain of myeloma protein 315 (L315), differs in amino acid sequence at many positions in the COOH-terminal domain from all other lambda chains whose sequences have been determined (called lambda1 chains). To determine whether chains of the L315 type (called lambda2) occur in normal mouse immunoglobulins, we synthesized the COOH-terminal peptides expected in tryptic digests of K, lambda1, and L315 and developed procedures to separate the S-carboxymethyl derivatives of these peptides. Peptide maps of tryptic digests of [14C]carboxymethyl-labeled L chains from normal serum immunoglobulins showed that about 1% of mouse 7S immunoglobulins have L chains of the L315 or lambda2 type.

Amino Acid Sequence↗
PubMedDate not supplied

Molecular parameters in melittin immunogenicity.

Based on immunogenicity studies, two T-cell epitopes in melittin were found to be functional in guinea pigs, one being centrally located, the other one residing in the C-terminal chain. In Balb/c mice only the central epitope was found to be active. A human T-cell clone was found by T-cell proliferation studies to employ strictly the C-terminal chain. Truncation of melittin peptides at the N-terminus did not markedly affect the capacity of guinea pigs to develop anti-IgG responses towards peptidic epitopes and towards a C-terminally attached haptenic group. Attachment of various substituents inside and outside the T-cell epitopic areas had no marked effect on antibody responses. In contrast, the substituents positioned within a T-cell epitope abolished T-cell proliferation. This difference between whole animal data and cellular in vitro responses is presently not understood.

Amino Acid Sequence↗
PubMedDate not supplied

Anti-phosphorylcholine antibodies with a preferred reactivity for either PC or PC-phenyl represent independent expressions.

Anti-hapten antibodies to phosphorylcholine(PC)-conjugated proteins can be divided into antibodies reacting preferentially with PC (group I) or with PC-phenyl (group II). We have selected two hybridomas producing group II-type anti-PC antibodies of the IgM and IgE classes, respectively. With one exception, NH2-terminal amino acid sequence analyses of the light chains are identical in their first 21 residues and similar to that of M460, but differ from that of group I-type light chains. These results suggest that PC-phenyl-specific group II antibodies are expressed independently of PC-specific group I antibodies.

Amino Acid Sequence↗
PubMedDate not supplied

Regulation of allergic inflammation by skin-homing T cells in allergic eczema.

BACKGROUND: In allergic inflammations of the skin, the pivotal role of CD45RO+ (memory/effector) T cells expressing the cutaneous lymphocyte-associated antigen (CLA) was demonstrated. In both atopic dermatitis (AD) and contact dermatitis (CD), T cells specific to skin-related allergens were confined to the CLA+ T cell population. Our research was aimed to further characterize these T cells in AD. METHODS: CD4+ and CD8+ subsets of CLA+ CD45RO+ T cells were purified from peripheral blood of AD patients and healthy control individuals. We studied, in vivo activation patterns, cytokine profiles, immunoglobulin isotype regulation and the influence of these cells on eosinophil survival and apoptosis. RESULTS: The CLA+ CD45RO+ T cells represent an in- vivo-activated memory/effector T cell subset as shown by surface expression of activation markers, spontaneous proliferation and a lower activation threshold via TCR/CD3 triggering. These cells contain and spontaneously release high amounts of preformed IL-5 and IL-13 but only very little IL-4 and IFN-gamma in their cytoplasm, as demonstrated by intracellular cytokine staining immediately after purification. Moreover, CLA+ memory/ effector T cells induce IgE production in B cells and enhance eosinophil survival by inhibiting eosinophil apoptosis in AD. In comparison, the CLA- population represents a resting memory T cell fraction, induces rather IgG4 in B cells and does not show any effect on eosinophil survival and apoptosis. CONCLUSION: Our results indicate that in-vivo-activated both CD4+ and CD8+ memory/effector T cells with skin-homing property play a specific and decisive role in the pathogenesis and exacerbation of AD. In contrast, resting memory T cells of atopic individuals retain normal, nonallergic immune functions.

Animals↗