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B Bogen

Publications and source records attributed to B Bogen.

68 records · Page 4Linked to original sources
PubMed1984

Determinant-specific regulation of T helper cell responses to murine lambda light chains by both H-2 and non-H-2 genes.

Previous work has revealed that the T helper cell (Th) responses to an antigenic determinant of V lambda 2(315) (called lambda 2.1) is regulated by both H-2 and non-H-2 genes. In the present study this was confirmed and extended to two other determinants, one shared between free lambda 2(315) and lambda 1(J558) (called lambda 2.2) and one unique for free lambda 1(J558) (called lambda 1.1). H-2 genes regulate the responses to the latter determinants, because BALB.B (H-2b) mice were low responders and BALB/c (H-2d) mice were high responders. Thus, the H-2d haplotype on BALB/c background was associated with high responder status. However, when the H-2d haplotype was examined on other genetic backgrounds than BALB/c, the animals could be classified as either intermediate or low responders, depending upon the non-H-2 background. This demonstrated that non-H-2 genes also influenced Th responses. Furthermore, C3H-H-2o, DBA/2 and B10.D2 mice (all H-2d) responded to only one (lambda 2.1) but not the other (lambda 2.2) of two determinants physically linked on the same polypeptide chain (lambda 2(315)). This indicated that the non-H-2 gene effect is capable of fine discrimination, i.e. the non-H-2 gene-mediated low responder phenotype may at least in part be due to failure of recognition of certain antigenic sites, like the H-2-linked Ir-gene defect. F1 hybrids responded to the same determinants as their parental strains; e.g., the BALB/c non-H-2 background exerted a dominant influence over the low responder background of C3H, B10 and DBA/2 strains.

Animals↗
PubMed1984

Specificity of antibody and helper T-cell responses to the isologous myeloma protein W3129 and its subunits.

The specificity of BALB/c antibodies and Th elicited by BALB/c myeloma protein W3129 (alpha, kappa) and its subunits was studied. Antibodies were detected with RIA and ELISA techniques. Th were demonstrated by their ability to augment a secondary anti-NIP antibody response in a Mitchison type assay of adoptive immunity. The major proportion of antibodies elicited by the complete W3129 was directed to an idiotypic determinant(s) that depended on assembled H + L chains. The determinant(s) was probably located in or near the antibody combining site because binding was hapten-inhibitable. A second minor antibody population bound an idiotypic determinant(s) on VW3129H expressed on isolated H-chain as well as on the complete myeloma protein. A third and very weakly reactive set of antibodies was specific for a C alpha antigenic site(s) which was expressed much more efficiently on free than on assembled alpha-chains. The antibody response to free kappa W3129 was directed to idiotypic determinants that were inaccessible in the complete molecule. By contrast, free kappa W3129 elicited Th that responded to an idiotypic determinant(s) on VW3129K; the determinant(s) was expressed on both the isolated chain and the complete W3129, suggesting that Th responded to an idiotope not recognized by B-cells. Priming with free alpha W3129 failed in four out of five experiments to induce Th that responded to the complete W3129, demonstrating that a major difference existed between VH and VL of W3129 regarding their immunogenicity for Th. Nevertheless, free alpha W3129 did elicit antibody responses that displayed high reactivity with the complete molecule, indicating that certain serologically defined antigenic sites on the surface of W3129 are also expressed on isolated alpha W3129. Thus, certain differences were detected as to the specificities of Th and B-cells for W3129 and its subunits since they recognized separate idiotopes located in the VL- or VH-region, respectively. The pattern of Th recognition of W3129 resembled that of another isologous myeloma protein, M315, but was unlike that of a third, J558, previously described from this laboratory.

Animals↗
PubMed1984

Antibody responses to lambda 1J558 and lambda 2315 light chains. Specificity and genetic regulation.

Specificity of BALB/c antibody responses to lambda chains of isologous myeloma proteins 315 and J558 was explored by enzyme-linked immunosorbent assay. lambda-chain binding antibodies were not detected when immunizing with assembled (H + L) myeloma proteins. However, relatively high titred IgG antibodies were elicited by free lambda 2(315) immunization. Antibodies were directed to 'hidden' determinants since binding was abrogated upon H + L assembly of chains. At least a portion of antibodies bound antigenic determinants in the variable region and cross-reacted with lambda 1 land lambda 3 chains. Free lambda 1J558 immunization induced low-titred, predominantly IgM antibodies that also only reacted with 'hidden' determinants. These determinants were most probably located in the constant (C) region and no cross-reaction to lambda 2 or lambda 3 was observed. An artefact of technical importance was noted: myeloma proteins exposed 'hidden' determinants on their lambda chains when coated directly to polystyrene walls. This artefactual exposition was lost when anti C-region antibody spacer molecules were inserted between the wall and the myeloma proteins. Antibody and T helper cell (Th) responses to free lambda 2(315) covaried significantly in various strains while antibody and Th responses to free lambda 1J558 did not. In some strains, weak antibody responses were detected without detectable Th.

Animals↗
PubMed1983

T helper cells recognize an idiotope located on peptide 88-114/117 of the light chain variable domain of an isologous myeloma protein (315).

Isolated variable region light chain 315 (VL-315), the VL domain of a myeloma protein of BALB/c origin, induces T cells of BALB/c (H-2d) mice that help the adoptive secondary anti-4-hydroxy-3-iodo-5-nitrophenylacetyl (NIP) antibody response to NIP-Fab315. The location of the epitope recognized by helper cells was examined with two fragments of VL-315, obtained by cleavage with cyanogen bromide at Met 87. Both N-terminal fragment 1-86 and C-terminal fragment 88-114/117 elicited BALB/c antibodies that bound to the respective fragments and to VL-315. By contrast, only fragment 88-114/117, which consists of the third hypervariable region, J region, and 5-7 amino acids of the C region, induced helper cells that augmented the anti-NIP response to NIP-Fab 315.

Animals↗
PubMed1983

Recognition of lambda 1 and lambda 2 murine light chains by carrier-specific isologous T helper cells; effect of L-H chain assembly.

Previous studies from this laboratory have revealed an antigenic site located on the variable domain of the lambda 2 light chain of BALB/c myeloma protein 315 (the V lambda 2(315) site). This site is recognized by conventional carrier-specific T helper cells (Th) of BALB/c mice and is expressed on both the free and assembled V lambda 2(315) domain. The present work defines two new antigenic sites associated with murine lambda chains. The first site was associated with free lambda 1-chain of myeloma protein J558. It was recognized by splenic Th from animals that had been primed with free lambda 1J558 in complete Freund's adjuvant; when transferred to irradiated animals the primed Th responded to a boost with (4-hydroxy-5-iodo-3-nitro-phenyl)acetate (NIP)-free lambda 1J558 in saline, but did not respond to NIP-complete J558 or NIP-free lambda 2(315). Priming with complete J558 failed to elicit Th that responded to NIP-free lambda 1J558. This determinant was therefore only expressed on the free (as opposed to the assembled) form of lambda 1J558, and it was not shared with free lambda 2(315). The second antigenic site was shared between free lambda 1J558 and free lambda 2(315). It was defined by free lambda 2(315)-primed Th which responded to a boost with NIP-free lambda 1J558. Since priming with free lambda 1J558 did not elicit Th that recognized NIP-free lambda 2(315), the cross-reaction was undirectional. The free lambda 2(315)-primed Th failed to respond to the complete J558, and M315-primed Th failed to respond to NIP-free lambda 1J558, indicating that the second (cross-reactive) antigenic site, like the first, was only expressed on free lambda chains. Completely reduced and alkylated (unfolded) free lambda 1J558 and free lambda 2(315) chains elicited Th that recognized native (folded) free chains. Thus, free lambda 1J558 bears two antigenic determinants recognized by Th, one private and a second shared with free lambda 2(315). Lambda 2(315) also bears two determinants, a cross-reactive one on free lambda 2(315) shared with free lambda 1J558, and a private one located on the V lambda 2(315) domain of the complete M315. The discussion is focused on possible explanations for the quenching of the two new lambda chain determinants upon light-heavy chain assembly and why, by contrast, the private V lambda 2(315) site is maintained in the complete M315.

Animals↗
PubMed1982

Monoclonal hybridoma antibodies to human amyloid related protein SAA.

Problems concerning isolation and characterization of the amyloid related serum protein SAA in a pure form prompted us to make monoclonal antibodies to the protein. Protein SAA isolated by gel filtration under dissociating conditions was used for immunization of BALB/c mice, and spleen cells from a mouse producing high titred antiserum to SAA were fused with cells from the mouse plasmacytoma line P3U1. Antibody specificity to various preparations of protein SAA was tested using an indirect enzyme-linked immunosorbent assay. Monoclonal antibodies with specificity for SAA were obtained in addition to antibodies which reacted with both SAA and the related amyloid protein AA. Antibodies specific for one of the apoC proteins of the lipoprotein fraction were also produced showing that the SAA preparation used for immunization was contaminated with apoC proteins.

Amyloid↗
PubMed1976

A computer-generated catalog of audiovisuals.

A computer-generated catalog of nonprint media is described. Examples are given of four access points to the data base: (1) main entry, (2) title, (3) MeSH terms, and (4) broad subject categories. The data input procedure is summarized. The AV catalog as the basis for a union list is evaluated, and finally, the catalog in relation to certain local problems is discussed.

Audiovisual Aids↗
PubMedDate not supplied

Immunoglobulin as a vehicle for foreign antigenic peptides immunogenic to T cells.

Antibody (Ab) molecules may serve as targeting vehicles for delivery of foreign antigenic peptides to antigen presenting cells (APC). An attractive strategy is to substitute segments between beta-strands of immunoglobulin (Ig) constant (C)-region domains with antigenic peptides. For this to work, the mutant Ab must maintain its conformation so that it can be secreted from transfected cells. Furthermore, the antigenic peptides must be excised by the processing machinery of APC and loaded onto major histo-compatibility complex (MHC) class II molecules. To test this, we have introduced a peptide of eleven amino acids (a.a.) as either of three different loops in the first C-region domain of the heavy (H) chain (CH1) of human IgG3. When the resulting mutant H chain genes were expressed in a fibroblast cell line equipped with proper class II molecules, the H chains were retained intracellularly, probably due to the light (L) chain deficiency of the fibroblasts. Nevertheless, by the endogenous class II processing pathway, presentation of the epitope to CD4+ cells was observed for all three mutants. The presentation efficiency, however, depended on the position of the peptide in the H chain. This could be due to influence of flanking sequences, which differ in the three loop replacement mutants. When L chain-expressing Chinese hamster ovary (CHO) lambda cells were transfected with the same constructs, two out of the three mutant Ig were secreted. The mutants had the expected antigen specificity and were recognized by anti-IgG Ab. When added exogenously to dendritic cell APC, the mutant IgG3 were processed, and the liberated foreign epitopes presented to T cells. The results suggest that the loops connecting beta-strands in the Ig fold may be replaced by foreign peptides, which upon processing become stimulatory to CD4+ T cells. Combined with the well-known targeting function of antibodies, this principle may be useful for construction of a new generation of vaccines.

Amino Acid Sequence↗
PubMedDate not supplied

Anti-class II antibodies, but not cytotoxic T-lymphocyte antigen 4-immunoglobulin hybrid molecules, prevent rejection of major histocompatibility complex class II-negative myeloma in T-cell receptor-transgenic mice.

We have previously shown that tumour-specific CD4+ T cells protect against subcutaneous injections of major histocompatibility complex (MHC) class II-negative MOPC315 myeloma cells. Here, we have interfered with the immunologic events that lead to successful rejection of MOPC315 challenges in T-cell receptor (TCR)-transgenic mice. The CD4+ T cells have a transgene-encoded TCR specific for a MOPC315 V-region idiotypic (Id) peptide presented on the MHC class II molecule E(d). A side-by-side comparison indicated that DNA-recombination-deficient TCR-transgenic mice were better protected against MOPC315 tumour development than recombination-sufficient counterparts, suggesting that B cells or endogenous TCR chains might facilitate tumour progression in this model. Intraperitoneal injections of E(d)-specific antibodies over a period of initial 24 days, abrogated protection against tumours in both strains of mice. By contrast, injections of anticostimulatory molecules (cytotoxic T-lymphocyte antigen 4-immunoglobulin hybrid molecules) had no effect. The findings demonstrate that tumour rejection depends on the presence of MHC class II molecules, despite the fact that MOPC315 tumour cells themselves do not express them. The results are consistent with the idea that secreted myeloma protein is processed and presented by class II+ antigen-presenting cells to Id-specific naïve CD4+ T cells that become activated and kill the myeloma cells by a bystander mechanism. While Id presentation on class II molecules is absolutely required for tumour rejection, costimulatory CD80/CD86 molecules might be dispensible in this process.

Animals↗