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Journal of Immunological Methods Mar 1983(1) Evidence has been presented that the detection of hapten-augmentable plaques indicates cells whose secretion of antibody had been blocked by the binding of...
Production of auto-anti-idiotypic antibody during the normal immune response. VI. Hapten augmentation of plaque formation and hapten-reversible inhibition of plaque formation as assays for anti-idiotype antibody.
(1) Evidence has been presented that the detection of hapten-augmentable plaques indicates cells whose secretion of antibody had been blocked by the binding of auto-anti-id to cell surface idiotypes. Because of the dependence of the assay on the affinities of the various species for one another, the number of hapten-augmentable plaques detected should be regarded as a minimal estimate of the number of cells whose secretion of antibody is inhibited by auto-anti-id. For confirmation that hapten-augmentable PFC are due to auto-anti-id 2 principal controls are important: (a) incubation of the spleen cell population with hapten prior to plaquing should remove the hapten-augmentable PFC; (b) the dialyzed supernate from hapten incubated cells should inhibit plaque formation in a hapten-reversible manner. (2) Evidence has been presented that hapten-reversible inhibition of plaque formation can serve as an assay for anti-id. Apparent false positive assays can result from the presence of anti-hapten antibody or antigen-antibody complexes; however, these apparent false positives are rarely reversed by hapten. Removal of anti-hapten antibody, by passage over an antigen immunoadsorbent, will eliminate this source of false positives and the procedure is recommended. False negative results can arise from mismatching of the anti-ids in the sample to be assayed and the idiotypes of the target cells used in the assay. This can result from shifts in idiotype expression related to age and time after antigen injection. False negatives can also result from the presence of idiotype-anti-id complexes in the sample to be assayed. This source of false negatives can sometimes be eliminated by passage of the sample through an antigen immunoadsorbent.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibody Formation; Autoantibodies; Haptens; Hemolytic Plaque Technique; Immunoglobulin Idiotypes; Immunosorbent Techniques; Mice
PubMed: 6339631
DOI: 10.1016/0022-1759(83)90258-2 -
Clinical Cancer Research : An Official... Nov 1995We generated an IgG1 murine monoclonal anti-idiotype antibody (Ab2) to a highly restricted T-cell antigen designated glycoprotein (gp) 37 that is found on T-cell...
We generated an IgG1 murine monoclonal anti-idiotype antibody (Ab2) to a highly restricted T-cell antigen designated glycoprotein (gp) 37 that is found on T-cell malignancies but not on normal cells. gp37 is identified by the murine monoclonal antibody SN2 (Ab1) against which the Ab2 was raised. Each of four patients with T-cell lymphoma predominantly confined to the skin received a minimum of four intracutaneous injections of aluminum hydroxide precipitated anti-idiotype murine monoclonal antibody (1 mg/injection) given every 2 weeks. For responding patients, injections were continued on a monthly basis. All tumors were measured along orthogonal major and minor axes, using a ruler and/or calipers, by the same observer. Tumor sizes were documented photographically. Three of the four patients developed specific idiotypic humoral immune responses, and two of the four patients also demonstrated idiotypic cell-mediated responses. Humoral responses included binding of the patients' sera to the anti-idiotype antibody as well as specific inhibition of binding of the SN2 antibody (Ab1) to the anti-idiotype antibody (Ab2). Anti-anti-idiotypic (Ab3) antibody from one patient's serum bound specifically to the gp37-positive cell line MOLT-4 and also to semipurified gp37 antigen. Cell-mediated responses were demonstrated by specific proliferative response to the aluminum hydroxide precipitated anti-idiotype antibody by patients' peripheral blood mononuclear cells. While three of the four patients had extensive disease and did not have clinical responses, one of the patients who had nine discrete skin tumors and peripheral blood involvement without other detectable disease had virtually complete disappearance of the tumors lasting over 11 months. Our results demonstrate that this particular anti-idiotype antibody can induce humoral and cellular immune responses, and at least in one patient led to a meaningful therapeutic response. Future trials should focus on immunocompetent patients with minimal disease.
Topics: Amino Acid Sequence; Animals; Antibodies, Anti-Idiotypic; Antibodies, Neoplasm; Antigens, Neoplasm; CD4-Positive T-Lymphocytes; Humans; Immunity, Cellular; Immunoglobulin G; Lymphoma, T-Cell, Cutaneous; Mice; Mice, Inbred BALB C; Molecular Sequence Data; Skin Neoplasms
PubMed: 9815923
DOI: No ID Found -
Clinical Immunology (Orlando, Fla.) Feb 2005Autoantibodies to ribosomal P protein (anti-P) are a specific hallmark of systemic lupus erythematous (SLE). Several authors found significant associations of anti-P...
Autoantibodies to ribosomal P protein (anti-P) are a specific hallmark of systemic lupus erythematous (SLE). Several authors found significant associations of anti-P antibodies with neuropsychiatric, hepatic, and renal disease. We now report the isolation by phage display of human anti-idiotype (Id) monoclonal antibody fragments as single-chain Fv fragment (scFv) against anti-P antibodies. The V gene repertoires were derived from the RNA obtained from the B cells of a SLE patient. Affinity-purified anti-P antibodies were used for the selection of bacterial clones producing anti-P-specific scFv antibody fragments and little reactivity with normal IgG and other IgG antibodies. The anti-Id antibody recognizes a public idiotope broadly cross-reactive with polyclonal anti-P antibodies and inhibited binding of anti-P to ribosomal P antigen in immunoassays and on Jurkat cells. The anti-Id scFv antibody fragment may have therapeutic implications in SLE. They may also be used as probes in the study of the structure of the idiotype.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; B-Lymphocytes; Enzyme-Linked Immunosorbent Assay; Flow Cytometry; Humans; Immunoblotting; Immunoglobulin Fragments; Immunoglobulin Idiotypes; Immunoglobulin Variable Region; Jurkat Cells; Lupus Erythematosus, Systemic; Peptide Library; RNA; Rabbits; Reverse Transcriptase Polymerase Chain Reaction; Ribosomal Proteins
PubMed: 15639646
DOI: 10.1016/j.clim.2004.03.015 -
Diabetes Research (Edinburgh, Scotland) Apr 1991Antibody directed against insulin carries idiotypic determinants that may induce an auto-anti-idiotype (anti-Id) antibody response. We describe a solid-phase enzyme...
IgG auto-anti-idiotype antibodies against antibody to insulin in insulin-dependent (type 1) diabetes mellitus. Detection by capture enzyme linked immunosorbent assay (ELISA) and relationship with anti-insulin antibody levels.
Antibody directed against insulin carries idiotypic determinants that may induce an auto-anti-idiotype (anti-Id) antibody response. We describe a solid-phase enzyme immunoassay which allows specific detection of IgG anti-Id directed against anti-insulin antibodies. Among 36 patients with type 1 diabetes, IgG anti-idiotype was detected in 21 (58%). An inverse significant correlation was found between titers of anti-idiotype and anti-insulin antibodies. These findings suggest that anti-idiotype antibodies may function to regulate the immune response to insulin. Whatever the mechanism of action of the anti-idiotype antibodies, we detected by ELISA, the clinical consequences and the theoretical implications of this determination may be important.
Topics: Animals; Antibodies, Anti-Idiotypic; Autoantibodies; Chickens; Child; Diabetes Mellitus, Type 1; Enzyme-Linked Immunosorbent Assay; Humans; Immunoglobulin G; Insulin Antibodies; Reference Values
PubMed: 1802485
DOI: No ID Found -
Fish & Shellfish Immunology Mar 2002Seven monoclonal anti-idiotype antibodies (mab2) were raised against mouse monoclonal antibody (mab1) 4A6. Identification of subclass showed that 1H5, 1D1, 2B12 and 2F12...
Seven monoclonal anti-idiotype antibodies (mab2) were raised against mouse monoclonal antibody (mab1) 4A6. Identification of subclass showed that 1H5, 1D1, 2B12 and 2F12 belonged to IgG2b, 2H12 and 1H12 to IgG2a and lE10 to IgG3. The titres of these mab2 ascitic fluids ranged from 1 x 10(-4)-1 x 10(-6). The capacity of the mab2 to inhibit the binding between the corresponding rabbit antiserum and Vibrio anguillarum was investigated with the competitive inhibition ELISA. The results showed that mab2 1D1, 1E10, 1H5 and 1H12 were able to inhibit this binding. Another experiment demonstrated that mab2 1D1, 1E10 and 1H5 might induce Balb/c mice to produce Ab3 and these Ab3 competed the same antigen epitopes with Ab1. These results indicate that mab2 1D1, 1E10 and 1H5 are likely to represent an internal image of V. anguillarum and may thus be described as Ab2-beta anti-idiotype antibodies. In protection experiments, Japanese flounders vaccinated with mab21D1, 1E10 and 1H5 showed significantly enhanced survival from challenge with V. anguillarum. Thus. mab21D1, 1E10 and 1H5 may have use as idiotype vaccines for fish in aquaculture.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibodies, Bacterial; Antibodies, Monoclonal; Aquaculture; Ascites; Female; Fish Diseases; Flounder; Injections, Intraperitoneal; Lethal Dose 50; Mice; Mice, Inbred BALB C; Time Factors; Vaccination; Vibrio; Vibrio Infections
PubMed: 11931021
DOI: 10.1006/fsim.2001.0370 -
PloS One 2016Vaccination with proteins mimicking GD2 that is highly expressed on neuroblastoma (NB) cells is a promising strategy in treatment of NB, a pediatric malignancy with poor...
Vaccination with proteins mimicking GD2 that is highly expressed on neuroblastoma (NB) cells is a promising strategy in treatment of NB, a pediatric malignancy with poor prognosis. We previously showed efficacy of ganglidiomab in vivo, a murine anti-idiotype (anti-Id) IgG1. In order to tailor immune responses to variable regions, we generated a new human/mouse chimeric anti-Id antibody (Ab) ganglidiximab by replacing murine constant fragments with corresponding human IgG1 regions. DNA sequences encoding for variable regions of heavy (VH) and light chains (VL) were synthesized by RT-PCR from total RNA of ganglidiomab-producing hybridoma cells and further ligated into mammalian expression plasmids with coding sequences for constant regions of human IgG1 heavy and light chains, respectively. We established a stable production cell line using Chinese hamster ovarian (CHO) cells co-transfected with two expression plasmids driving the expression of either ganglidiximab heavy or light chain. After purification from supernatants, anti-idiotypic characteristics of ganglidiximab were demonstrated. Binding of ganglidiximab to anti-GD2 Abs of the 14.18 family as well as to NK-92tr cells expressing a GD2-specific chimeric antigen receptor (scFv(ch14.18)-zeta) was shown using standard ELISA and flow cytometry analysis, respectively. Ganglidiximab binding affinities to anti-GD2 Abs were further determined by surface plasmon resonance technique. Moreover, binding of anti-GD2 Abs to the nominal antigen GD2 as well as GD2-specific Ab-mediated cytotoxicity (ADCC, CDC) was competitively inhibited by ganglidiximab. Finally, ganglidiximab was successfully used as a protein vaccine in vivo to induce a GD2-specific humoral immune response. In summary, we report generation and characterization of a new human/mouse chimeric anti-Id Ab ganglidiximab for active immunotherapy against NB. This Ab may be useful to tailor immune responses to the paratope regions mimicking GD2 overexpressed in NB.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antibody Affinity; CHO Cells; Cancer Vaccines; Cricetinae; Cricetulus; Cytotoxicity, Immunologic; Humans; Immunotherapy, Active; Killer Cells, Natural; Mice; Neuroblastoma
PubMed: 26967324
DOI: 10.1371/journal.pone.0150479 -
The AAPS Journal Jan 2024Non-neutralizing anti-idiotype antibodies against a therapeutic monoclonal antibody (mAb) play a crucial role in the creation of total pharmacokinetic (PK) assays and...
Non-neutralizing anti-idiotype antibodies against a therapeutic monoclonal antibody (mAb) play a crucial role in the creation of total pharmacokinetic (PK) assays and total target engagement (TE) assays during both pre-clinical and clinical development. The development of these anti-idiotype antibodies is challenging. In this study, we utilized a hybridoma platform to produce a variety of anti-idiotype antibodies against GSK2857914, a humanized IgG1 anti-BCMA monoclonal antibody. The candidate clones were evaluated using surface plasmon resonance (SPR) and bio-layer interferometry (BLI) for binding affinity, binding profiling, matrix interference, and antibody pairing determination. We discovered that three anti-idiotype antibodies did not prevent BCMA from binding to GSK2857914. All three candidates demonstrated high binding affinities. One of the three exhibited minimal matrix inference and could pair with the other two candidates. Additionally, one of the three clones was biotinylated as a capture reagent for the total PK assay, and another was labeled with ruthenium as a detection reagent for both the total PK assay and total TE assay. The assay results clearly show that these reagents are genuine non-neutralizing anti-idiotypic antibodies and are suitable for total PK and TE assay development. Based on this and similar studies, we conclude that the hybridoma platform has a high success rate for generating non-neutralizing anti-idiotype antibodies. Our methodology for developing and characterizing non-neutralizing anti-idiotype antibodies to therapeutic antibodies can be generally applied to any antibody-based drug candidate's total PK and total TE assay development.
Topics: Antibodies, Monoclonal; Biological Assay; Immunoglobulin G; Surface Plasmon Resonance; Antibodies, Anti-Idiotypic
PubMed: 38267774
DOI: 10.1208/s12248-024-00892-z -
Veterinary Microbiology Jul 2001A monoclonal antibody (Mab 4.52) raised against Mycoplasma capricolum subsp. capripneumoniae (Mccp) cell lysate was used as a template to obtain substitute antigens...
Phage displayed peptides and anti-idiotype antibodies recognised by a monoclonal antibody directed against a diagnostic antigen of Mycoplasma capricolum subsp. capripneumoniae.
A monoclonal antibody (Mab 4.52) raised against Mycoplasma capricolum subsp. capripneumoniae (Mccp) cell lysate was used as a template to obtain substitute antigens recognised by its paratope. Two approaches were investigated: a 17-mer random peptide library displayed on the surface of a filamentous phage was screened by panning on the immobilised Mab 4.52 and anti-idiotype antibodies were generated by immunising a chicken with the F(ab')(2) fragments of the antibody. Analysis of the peptide sequences displayed by the isolated phages identified two peptides. Both contained two cysteine residues and had identical or similar amino acids in positions 5 (P), 8 (I/L) and 13 (L). The fusion phages were also recognised by Mab 4.52 in enzyme-linked immunosorbent assay (ELISA) and binding was shown by surface plasmon resonance. One of the peptides was a markedly better inhibitor (67%) of the binding of Mab 4.52 to its original antigen than the other (20%) at 1mg/ml. After absorption, to remove isotypic and allotypic reactivities, the anti-idiotype IgY was specifically recognised by Mab 4.52 in ELISA and was able to inhibit its binding to the original antigen, whereas anti-idiotype antibodies raised against a bluetongue virus-specific antibody had no effect. In spite of unequivocal binding of the anti-idiotype antibodies and the fusion phages to the paratope of Mab 4.52, goat antisera appeared not to react with either of the surrogate antigens. In contrast, the test sera bound to the original antigen suggesting that Mab 4.52 does not recognise exactly the same antigenic site as antibodies in the goat antisera.
Topics: Amino Acid Sequence; Animals; Antibodies, Anti-Idiotypic; Antibodies, Monoclonal; Antigens, Bacterial; Chickens; DNA, Bacterial; Enzyme-Linked Immunosorbent Assay; Epitopes; Female; Immunoglobulins; Molecular Sequence Data; Mycoplasma; Mycoplasma Infections; Peptide Library; Sequence Analysis, DNA; Surface Plasmon Resonance
PubMed: 11376960
DOI: 10.1016/s0378-1135(01)00338-8 -
Cellular Immunology Sep 1986Three lines of evidence are presented which suggest that autoimmune-prone mice are deficient in the production of auto-anti-idiotype antibody during their immune... (Comparative Study)
Comparative Study
Three lines of evidence are presented which suggest that autoimmune-prone mice are deficient in the production of auto-anti-idiotype antibody during their immune response to trinitrophenylated Ficoll (TNP-F). NZB, MRL lpr/lpr and older BXSB male mice have no hapten-augmentable plaque-forming cells (PFC). Hapten-augmentable PFC have been previously shown to be cells whose secretion of antibody has been inhibited by the binding of auto-anti-idiotype antibody to cell surface idiotype. Sera from TNP-F immunized NZB mice lack PFC inhibiting activity (anti-idiotype antibody). Spleen cells from TNP-F immune NZB mice fail to transfer anti-idiotype antibody-mediated suppression to naive mice as do spleen cells from immune non-autoimmune-prone mice. Taken together these data suggest that autoimmune-prone mice are deficient in auto-anti-idiotype antibody-mediated downward regulation of their immune responses. It was further shown that the immune response of NZB mice to TNP-F shows a slower decline in splenic PFC and a greater heterogeneity of PFC affinity than do the responses of non-autoimmune-prone strains. Since athymic (nude) mice, which were previously shown to be defective in the production of auto-anti-idiotype antibody, also show a slower decline in splenic PFC and an increased heterogeneity of PFC affinity, it is suggested that these peculiarities of the immune responses of autoimmune-prone and athymic mice are also the consequences of the lack of auto-anti-idiotype antibody-mediated down-regulation.
Topics: Animals; Antibodies, Anti-Idiotypic; Antibody Affinity; Autoantibodies; Autoimmune Diseases; Immunization, Passive; Immunoglobulin Idiotypes; Immunologic Deficiency Syndromes; Male; Mice; Mice, Inbred AKR; Mice, Inbred BALB C; Mice, Inbred NZB; Mice, Nude; Spleen
PubMed: 3489534
DOI: 10.1016/0008-8749(86)90141-3 -
Cellular Immunology Jan 1988Specific tolerance to phosphorylcholine (PC) can be induced in BALB/c mice by neonatal injection with either pneumococcal C-polysaccharide (PnC) containing PC or...
Specific tolerance to phosphorylcholine (PC) can be induced in BALB/c mice by neonatal injection with either pneumococcal C-polysaccharide (PnC) containing PC or anti-TEPC-15 idiotype (T15id) antibody which recognizes the predominant idiotype of anti-PC antibody of BALB/c mice. Suppressor T cells (Ts) induced after treatment with anti-T15id antibody react with the T15id and PnC-induced Ts cells appear to recognize PC. A brief incubation of anti-id-induced, T15id-specific Ts with PnC-induced, PC-reactive Ts resulted in complete cancellation of their suppressor functions. However, both types of Ts were present in mice neonatally injected with mixtures of PnC and anti-T15id antibody. Neutralization experiments using either PnC-induced or anti-id-induced suppressor T cells strongly suggest that only one of the Ts cell types is functionally dominant in those mice: most frequently, T15id-specific Ts cells. The suppressor function of the other population is detectable only when the predominant Ts cell population is removed by anti-id or monoclonal IgM anti-PC (SP45) plus complement. However, both suppressor activities are completely eliminated when one of the Ts populations is removed by adherence to either antigen or T15id. These results suggest that mice neonatally injected with a mixture of antigen and anti-id antibody possess both types of suppressor T cells, yet only one type is functionally dominant.
Topics: Animals; Animals, Newborn; Antibodies, Anti-Idiotypic; Antibody Formation; Immune Tolerance; Immunoglobulin Idiotypes; Mice; Mice, Inbred BALB C; Phosphorylcholine; Receptors, Antigen, T-Cell; Spleen; T-Lymphocytes, Regulatory
PubMed: 2962743
DOI: 10.1016/0008-8749(88)90064-0