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The sera of 187 patients from across the leprosy spectrum were screened for the expression of the PR4 idiotype, which was first identified on a human hybridoma-derived monoclonal antibody from a patient with leprosy and found to react with the mycobacterium leprae phenolic glycolipid and a variety of polynucleotides. Sixty per cent (51 out of 85) of patients with lepromatous leprosy (LL), 66% (33 out of 49) with borderline lepromatous (BL) disease, 47% (14 out of 30) with borderline tuberculoid (BT) leprosy, and 56% (13 out of 23) of tuberculoid (TT) patients were found to have significantly elevated titires of the PR4 idiotype in their sera compared with endemic controls, irrespective of the presence or absence of endemic malaria. Sera from 52 patients with tuberculosis were also sereened as a control for mycobacterial infection. The PR4 idiotype was significantly elevated in 37% (19 out of 52) of these patients. No correlation between idiotype and serum immunoglobulins IgG and IgM was found, indicating that the concentrations of idiotype levels in sera were not merely a reflection of changes in serum immunoglobulin levels. It is hypothesized that the expression of the PR4 idiotype is due to certain germline genes preferentially expressed rather than being the result of polyclonal B cell activation. [ABSTRACT FROM AUTHOR]

We investigated the role of MRL T cells in the induction of anti-Sm antibodies and Y2 idiotype. Four injections of Sm antigen in Freund's complete adjuvant were required to induce peak amounts of specific anti-Sm antibody In young BALB/c and MRL/ + mice. The Y2 idiotype was expressed in MRL/+ mice but not in BALB/c mice. Expression of both anti-Sm., predominantly IgG2a heavy chain, and Y2 idiotype was augmented in MRL/+ mice after two injections of Sm if, prior to immunization, mice received splenic T cells from naive MRL/lpr or immunized, but not naive MRL/+ mice. These results suggest that the lpr gene contributes to the ability of autoimmune T cells to augment the anti-Sm antibody response. Treatment of primed MRL/+ donor T cells with anti-CD4, but not anti-CD8. antibodies and complement removed the ability to augment anti-Sm antibody production, ln contrast, augmentation of Y2 idiotype production was abrogated by pretreatment of donor T cells with either anti-CD4 or anti-CD8. These results suggest that, while MRL/+ CD4+ T cells play an important role in anti-Sm antibody production, additional interaction between and CD8+ T cells augments Y2 expression. [ABSTRACT FROM AUTHOR]

We have recently produced a series of human monoclonal antibodies reacting with cardiolipin. One of these, H3, a polyspecific IgM/k derived from a normal individual, was used to raise mouse monoclonal antibody to its idiotype. Two anti-idiotypic antibodies, S2.9 (IgG2b) and S2.10 (IgM) were selected for their specific reaction with H3. S2.9 did not react with five other human monoclonal antibodies of IgM/k class despite the fact that these shared some antigen-binding characteristics with H3. S2.9 was able to block the binding of H3 to all of its cross-reactive antigens including cardiolipin, while S2.10 was not. S2.9 was equally efficient in blocking the binding of H3 to three of its cross- reactive antigens, cardiolipin, diphtheria and tetanus toxoids; greater than 90% inhibition could be achieved at an equimolar ratio of H3 to S2.9. The anti-idiotype S2.9 was used to demonstrate the presence of the H3 idiotype in serum. This idiotype was found in amounts greater than that seen in 42 normal individuals, in 30 of 36 patients with systemic lupus erythematosus (SLE), eight of 20 patients with rheumatoid arthritis (RA), 8 of 20 patients with Felty's syndrome as well as 10 of 23 patients with syphilis. Not one of nine patients with drug-induced lupus syndrome had abnormal levels. In patients with SLE and Felty's syndrome there was a good correlation between the amount of anti-cardiolipin antibodies and the amount of H3 idiotype (rs =0.70 and 0.69 respectively). No such correlation was found in sy&pgrave;hilitics or in patients with RA. In patients with SLE the H3 idiotype was present on IgM and IgG anti-cardiolipin antibodies. In 15 of 16 SLE sera with high levels of cardiolipin antibody, S2.9 blocked binding of serum antibodies to cardiolipin by 13- 72, with a mean value of 49%. One patient had a high level of anti-cardiolipin antibody which could not be blocked by S2.9. These results indicate that a mouse monoclonal antibody which reacts with an idiotope in the antigen-binding region of a naturally-occurring phospholipid antibody also defines a common idiotype of anti- cardiolipin antibodies in patients with autoimmune disease. [ABSTRACT FROM AUTHOR]

Isoelectric focusing of serial bleeds from patients with Hashimoto's thyroiditis was carried out and thyroglobulin (Tg autoantibodies visualized using 125Habelled Tg followed by autoradiography. Although the spectrotype of these antibodies was polyclonal and varied from patient to patient, each individual's spectrotype remained constant during the disease. Similar results were obtained if immunoblots were stained with rabbit anti-idiotype (anti-Id) raised to these autoantibodies. Using radioimmunoassay (RIA), it is shown that the levels of Id remain constant over several years whether assayed on crude immunoglobulin (Ig) fractions or affinity-purified anti-Tg. Therefore, once established, the autoimmune disease appears to be stable in terms of autoantibody spectrotype and idiotype in the patients studied. [ABSTRACT FROM AUTHOR]

The public idiotype Id-16/6 and the public idiotope Id-LLa were originally defined on the same human monoclonal anti-DNA antibody, but they are also known to occur separately on other anti-DNA antibodies. We sought the presence of these immunoglobulin variable region markers in purified immunoglobulins from the serum of nine patients with systemic lupus erythematosus (SLE) and 33 healthy donors. Sera from five patients were positive for Id-16/6. and five were positive for Id- LLa. The immunoglobulin preparations were passed over a Sepharose-Id-16/6 column in order to recover auto-anti-idiotypes. An eluate of that column was obtained from the immunoglobulin preparation of one patient whose serum was Id-16/6+and Id-LLa-. This eluate was shown by competition assay to bind to IdLLa. This is the first demonstration of spontaneously arising human auto-anti-idiotypes against a specific idiotypic system in SLE. The results suggest that antibodies against the Id-LLa idiotope may play a role in immunoregulation. [ABSTRACT FROM AUTHOR]

Using hybridoma technology we produced monoclonal antibodies (MoAb) to idiotypic determinants on human anti-cardiolipin antibodies purified from a patient with SLE. Hybridomas were screened by inhibition of cardiolipin binding activity of sera from patients with SLE. Seven hybridomas were selected, two of which were studied extensively. Sera from a number of patients with SLE were found to share idiotypic determinants. This cross-reacting idiotype was not detectable on anti-cardiolipin antibodies in syphilis sera. The cross-reacting idiotype was present in sera with anti-ssDNA antibodies even though some of these sera had no anti-cardiolipin antibodies. We propose that these MoAb may recognize a regulatory idiotype. [ABSTRACT FROM AUTHOR]

The possibility that shared idiotypes may be present on antibodies of different specificities was explored using sera from 13 patients with systemic lupus erythematosus. Eleven sera had anti-DNA and seven carried the 16/6 idiotype (ID). Two of the sera with 16/6 ID also had lymphocytotoxic antibodies, the activity of which was blocked by antibody to the 16/6 ID. Our studies reveal that 16/6 ID is present on two antibodies with different binding specificities. [ABSTRACT FROM AUTHOR]

The article reports that in spite of its imperfections, vaccination remains the best answer to infectious diseases. Vaccination has been mainly responsible for the eradication of smallpox and for the control of yellow fever, poliomyelitis, and German measles in the human population, and of Newcastle disease, foot-and-mouth disease and Marek's disease in domestic animals. The art of deliberate immunization against infections has been practiced for centuries but the mechanisms of protective immunity were not fully appreciated until the advent of modern immunology.

The monoclonal immunoglobulin (Ig) (M-component) secreted by the tumour plasma cells in multiple myeloma (MM) has specific antigenic determinants (idiotypes; id) that can serve as tumour-specific antigens. The intact Ig molecule is a weak antigen, and small fragments of id protein might be more immunogenic for the induction of id-specific immunity. Dendritic cells (DC) have attracted attention as the most efficient antigen-presenting cells and promising adjuvants for immunotherapy in tumours. In this study the in vitro T-cell response against F(ab′)2 and Fab fragments, heavy and light chains of the M-component was examined in five patients with MM clinical stage I. All fragments were able to stimulate T cells but F(ab′)2 or Fab fragments and heavy chains induced a stronger response than light chains. DC induced a significantly stronger id-specific immune response than monocytes. Moreover, with DC as antigen-presenting cells, a predominant interferon (IFN)-γ (type-1 T-cell) response was seen in all patients. Both IFN-γ and interleukin (IL)-4 (type-1 and type-2 T-cell) responses were noted when monocytes were used. Our study suggests that DC pulsed with idiotypic fragments such as F(ab′)2 fragment and heavy chain can be used for the induction of type-1 anti-idiotypic T-cell response for immunotherapy in MM. [ABSTRACT FROM AUTHOR]

Mouse monoclonal antibody is not well fitted to destroying tumour cell targets. Complement and cellular effectors are inefficiently recruited, the cells can undergo antigenic modulation, antigen-negative mutants can arise, and the tumour-bearing subject can amount an immune response against the therapeutic antibody. This paper describes the preparation of two chimeric antibody derivatives designed to cirvumvent some of these problems. The first derivative is FabFc, prepared by linking Fab'γ from monoclonal antibody to Fcγ from human IgG. The bismaleimide linking agent forms a thioether bond with an SH group released by reduction of SS bonds in the hinge of each constituent. The second derivative is bisFabFc, formed by a bismaleimide in this case joining two FabFc molecules via a free SH in the Fc hinge of each. As regards antibody activity against target cells bisFabFc can be univalent (one active, one inactive Fab arm), bivalent, or bispecific (with each Fab arm directed against a different cell surface antigen). Its juxtaposed dual Fc regions are designed to promote cooperative binding of effectors. Some preliminary characterization in vitro has employed antibodies of anti-idiotypic specificity directed against guinea-pig LC leukaemic B lymphocytes. The parent mouse IgG1 antibody failed to invoke complement cytotoxicity or antibody-dependent cellular cytotoxicity, while the chimeric derivatives yielded good killing in both systems. In complement lysis bivalent bicFabFc outperformed univalent, which in turn outperformed the FabFc monomer. [ABSTRACT FROM AUTHOR]

Dendritic cells (DC) are extremely potent antigen presenting cells, uniquely capable of sensitizing naive T cells to protein antigens and eliciting antigen specific immune responses. Studies of human DC isolated from peripheral blood indicate that these cells can be used to stimulate and expand antigen specific CD4+ and CD8+ T cells, in vitro. On the basis of these findings we have initiated pilot clinical studies to investigate the ability of DC pulsed ex vivo with tumor associated proteins to stimulate host anti-tumor immunity when re-infused as a vaccine. In the first such study DC pulsed with tumor derived idiotype protein were infused into patients with low grade malignant B cell lymphoma who had failed conventional chemotherapy. The majority of treated patients developed T cell mediated anti-idiotype immune responses and some of the patients experienced tumor regression. These results suggest that DC based immunotherapy is a potentially useful approach to B cell lymphoma and raises the possibility that the approach may prove useful in the treatment of other tumors as well. [ABSTRACT FROM AUTHOR]

The idiotype is a product of malignant plasmacells and can be identified in a highly specific manner by antiidiotypic antisera. The idiotype is usefull as a tumor-specific marker in myelomas and has been worked with in different problems. The main methods used were: immunofluorescence, internal labeling of immunoglobulins with radioactiv-labeled aminoacids, radio-immunobinding-inhibition assay. The results are as follows: 1. Idiotype bearing precursor-cells are detectable in the periphery of myeloma patients. But in our experimental approach we were not able to demonstrate, that these cells are infact synthesizing the idiotype although the methode has been proved to be sensitiv enough. 2. The idiotypic proportion of the total immunoglobulin-fraction (=M-component in the electrophorisis) in myelomasera ranges between 40 and 90%. This percentage remains in the order of 40% even in complete remission. 3. The idiotype as tumorspecific marker is only usefull as an early detector of relapse in patients with complete remission. [ABSTRACT FROM AUTHOR]

In this paper, the results of some recent studies on idiotype-specific T cells in human multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS) are discussed. By using different in vitro measurements such as 3H-thymidine incorporation and ELI-SPOT assay, idiotype-specific T cells have been demonstrated in most of MM and MGUS patients. Based on the cytokine-secretion profiles, idiotype-specific T cells were found to comprise both Th1 and Th2 cells. A Th1 type immunity was found preferentially in indolent disease and a Th2-like response predominated in advanced MM, suggesting a specific T-cell regulation of the tumor B-cell clone. The mode of T-cell recognition of id determinants on M-components has been studied. We found that idiotype-specific T cells recognized processed id determinants presented by MHC class II (HLA-DR) molecules on APC. B cells were much more efficient APC than monocytes. With the aim to induce or to amplify an idiotype-specific T-cell response, we have immunized MM patients with the autologous M-component precipitated in aluminum. Three out of the five patients showed an induction of specific cellular and humoral immunity. Nevertheless, the role for such immunity in controlling the tumor clone remains to be established. [ABSTRACT FROM AUTHOR]

We have investigated antigen-independent modulation of immune responses by monoclonal antibodies directed against both viral and nonviral antigens. BALB/c mice were immunized with monoclonal IgM (i.e. Ab1) specific for either Moloney murine leukemia virus-induced cell surface antigen (MCSA) or the hapten 2,4-dinitrophenyl (DNP). Injection with either Ab1 activated a functional idiotypic (Id) network as evidenced by production of both anti-Id (Ab2) antibodies and anti-anti-Id (Ab3) antibodies. A subset of induced Ab3 (designated Ab1), exhibited specificity for antigen (virus or DNP). In mice immunized with anti-Id antibodies (Ab2), production of Ab3 and Ab1′ was also observed. In the MCSA system, antibody-induced Ab1′ responses were effective in protecting mice from tumor development upon subsequent challenge with live virus. Furthermore, antigen-independent modulation of immunity to both viral and nonviral antigens was found to be thymus-dependent. Similar findings in other viral systems suggest that antibody-induced activation of Id networks may prove a viable alternative vaccine strategy that can elicit antigen-specific responses, and in some cases protection, in the apparent absence of exposure to antigen. [ABSTRACT FROM AUTHOR]

In this study, the contribution of idiotype-positive antitumor antibodies (anti-Id) in protective tumor immunity was investigated. We have previously shown that among various anti-Id generated and typed as the internal-image Ab2 of the tumor-associated antibody (TAA) gp52, only 2F10 antibody induces protective immunity. Increase of the 2F10 idiotope in sera of tumor-bearing mice correlated with long-term survival, while in mice with short survival the circulating 2F10 idiotype decreased. 2F10 Ig were purified from sera of tumor-bearing mice with longterm survival and the amount of 2F10 anti-TAA antibodies was determined. Only about 3% of 2F10 antibodies are 2F10 anti-TAA. Hybridomas were generated from a 2F10 high mouse with spontaneous tumor regression. Only 2 out of 52 tumor-specific hybridomas were 2F10. These results suggest that the protective effect induced by 2F10 vaccination may not be directly mediated by 2F10 antibodies but indirectly through the stimulation of a 2F10-specific cellular immune response. [ABSTRACT FROM AUTHOR]

Lymphocytes from two patients with multiple myeloma stage I and one patient with monoclonal gammopathy of undetermined significance were found to proliferate specifically in response to low concentrations of F(ab′) fragments of the autologous M component. T cell clones isolated from repeatedly stimulated cultures bound specifically the autologous idiotype and proliferated after addition of soluble idiotype and exogenous interleukin-2. The majority of clones were CD8 and showed negligible staining for CD4. Idiotype-binding clones could not be isolated from cultures of lymphocytes from a healthy control stimulated under the same conditions. The study provides support for the existence of idiotype-reactive T cells in monoclonal gammopathies. Such cells might have a regulatory role on the tumour cell clone and may be important for a future therapeutic approach. [ABSTRACT FROM AUTHOR]

Methods for producing syngeneic anti-idiotypic antibodies, with emphasis on immunization and screening methodologies, are described. These methods should result in the production of monoclonal antibodies that have structural conformations similar to the initiating epitope of the antigen. [ABSTRACT FROM AUTHOR]

The origins and regulation of autoantibodies in SLE may involve idiotypic cell interactions. The purpose of this study was to determine if SLE patients have T cells reactive with the idiotopes of autoantibodies. Sequences of the variable regions of two DNA-binding autoantibodies (Vλ of antibody B3 and VH of 9G4) were selected according to the predicted location of their idiotypes defined previously by anti-idiotypic antibodies. The sequences were prepared as synthetic 16mer peptides (idiopeptides). Peripheral blood mononuclear cells were prepared from SLE patients (n = 28) and controls (n = 13) and put into multiple microcultures with idiopeptide for 6 days. The frequency of responding cultures was determined as those incorporating thymidine at levels above the mean plus three standard deviations of the control cultures lacking peptide. Of the 28 lupus patients, six responded to B3 idiopeptide and five to the 9G4 idiopeptide. Some patients responded to other idiopeptides, but only one normal individual responded to each reference peptide. The difference between the patient and control responses to all idiopeptides was significant by χ2 analysis (P = 0.025). We conclude that patients with SLE show evidence of sensitisation of T cells to idiotopes of autoantibodies. Such anti-idiotypic T cells could either provide idiotype-specific help or suppression for autoantibody responses in SLE. [ABSTRACT FROM PUBLISHER]

We describe a human monoclonal antibody designated WRI 176 β and a common idiotype that it carries. This antibody was derived from the spleen of a patient with SLE. WRI 176 is an IgM kappa monoclonal reacting with ssDNA, dsDNA, poly(dT) and it is likely that mAb WRI 176 β is a representative of the so-called natural autoantibodies. The common Id designated WRI 176 Id β is located on the heavy chain of the mAb WRI 176 β molecule and appears to be located outside the binding site. Sequence analysis of the WRI 176 β heavy chain showed it to be highly homologous (97.3%) with a germline gene 56PI derived from a human fetus. In a retrospective analysis, although 44% of SLE patients had raised levels of the WRI 176 β no correlation was found with the activity of the disease. The idiotype was also expressed frequently in a range of autoimmune rheumatic and infectious diseases and in some healthy first-degree relatives of SLE patients. [ABSTRACT FROM PUBLISHER]

Many studies have shown that DNA-reactive autoantibodies share cross-reactive public idiotypes that are defined, usually, by single anti-idiotype reagents. Because anti-idiotype antibodies or antisera will be limited in their ability to detect all the idiotopes of a particular antibody, their use will tend to underestimate the full extent of idiotype sharing between different antibodies. In order to define more comprehensively the extent of idiotype sharing in DNA autoantibodies, a panel of DNA-binding monoclonal autoantibodies from lupus mice was examined with a range of anti-idiotype antisera prepared in rabbits (five sera), guinea pigs (four sera) and a sheep. Each idiotype was detected on more antibodies than its original reference monoclonal antibody, and idiotopes of each were also present on serum immunoglobulins from lupus mice. Of 23 monoclonal antibodies 65% reacted with one or more of the anti-idiotype reagents. On these criteria, all the idiotypes were public; none was private in its expression.In about half the cases the idiotypes were located in or near the antigen-binding sites of the antibodies, but a direct relationship to specificity was not obvious except in the case of Id.228 present on antibodies with a relatively high affinity for single-stranded DNA. In other cases there was no obvious relationship between idiotype and specificity. Antibodies from the same mouse did not each express the same array of idiotopes. None of the idiotypes was restricted to either (NZB x NZW)F1 or MRL/Mp-lpr/lpr mice, but there were differences between the strains. In the former, the expression of idiotype Id.88 notably decreased with age, whereas it rose with age in mice of the latter strain. The extent of sharing of the idiotypes of these DNA antibodies indicates that the great majority of the antibodies are related to each other idiotypically. From these studies, it is clear that the definition of idiotype sharing can be achieved comprehensively only if antibodies against many idiotopes are used. [ABSTRACT FROM PUBLISHER]

Monoclonal antibody (mAb) BEG-2 is a dsDNA binding IgM λ derived from a 12-week human fetus. Two binding site idiotypes (BEG-2 Id α and BEG-2 Id β) have been defined with the use of polyclonal rabbit anti-idiotypic anti-serum. BEG-2 Id α is located on the λ light chain and has been described previously. The BEG-2 Id β is present on the μ heavy chain. By means of a direct binding ELISA, BEG-2 Id β has been identified on EBV-derived mAbs from human fetal liver or spleen (5%), human cord blood (2.7%) and adult peripheral blood (1%). In addition, the Id is present on 8.5% of adult spleen-derived hybridoma antibodies and 6% of RA synovium-derived hybridoma antibodies. In all populations the presence of the Id is associated with binding to DNA and other polyanions. Competition indicated that the Id was located at or near the antigen-binding site on these molecules. To explore the structural basis of this binding, a major part of the BEG-2 chain was sequenced and found to be encoded by a member of the VH4 family joined to a variant of JH5 by a very short Diversity or N region. Of the BEG-2 Id β positive mAbs for which the VH family has been determined, five are encoded by VH4 and two are encoded by VH6, but none is encoded by other families. Thus, the BEG-2 Id β identifies a set of polyreactive antibodies that are common in fetal life, into adulthood and are encoded by VH6 and, a subset of VH4 genes. [ABSTRACT FROM PUBLISHER]

Data from both animal and clinical studies suggest that anti-idiotype antibodies deposited in glomeruli may be involved in the pathogenesis of glomerulonephritis. This study was conducted to examine the role of a hybridoma-AB1-2-derived IgG anti-T15 idiotype (IgG anti-T15) in the immunopathogenesis of a short-term experimental IgA nephropathy. BALB/c mice (12/group) were administered intravenously with: (1) an equal mass (1 mg) of T15-hybridoma-derived IgA antiphosphorylcholine (PC) and PC-conjugated bovine serum albumin (BSA-PC) antigen; (2) 1 mg of IgA anti-PC, 1 mg of BSA-PC antigen, and 3 mg of IgG anti-T15, or (3) 1 mg of BSA-PC antigen alone. The mice were sacrificed 6 h after the injection. A 6-hour clearance study was performed. The initial phase of elimination of BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC/IgG anti-T15 or those receiving the antigen alone was significantly faster than that in those receiving IgA anti-PC/BSA-PC (p < 0.001). There was no significant difference in the elimination rate of BSA-PC antigen between mice receiving IgA anti-PC/BSA-PC/IgG anti-T15 and those receiving BSA-PC antigen alone. The late phases of elimination of the BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC/IgG anti-T15 showed somewhat similar to those of BSA-PC antigen in mice receiving IgA anti-PC/BSA-PC. Moreover, mice injected with IgA anti-PC/BSA-PC/IgG anti-T15 showed a significantly less glomerular BSA-PC antigen deposition than those injected with IgA anti-PC/BSA-PC (positive control), as demonstrated by light microscopy, autoradiography, and immunohistochemistry (each p < 0.001). It is inferred that the injected IgG anti-T15 could react with the IgA anti-PC in vivo, directly interfering with immune complex formation by the IgA anti-PC and BSA-PC antigen, thereby resulting in diminished glomerular deposition of the BSA-PC antigen. These findings suggest that an anti-idiotype antibody may be protective in the immunopathogenesis of IgA nephropathy, because of its inhibitory effect on glomerular trapping of an antigen. [ABSTRACT FROM AUTHOR]

In an investigation of the immunoglobulin idiotypic expression of non-tumour and neoplastic B lymphocytes in situ, fresh-frozen specimens of reactive tonsils, lymph nodes and B-cell malignant lymphomas (B-MLs) from Japanese patients were studied immuno-histochemically with 39 different anti-idiotype antibodies. In reactive lymphoid tissues, while idiotype-bearing cells were largely distributed sparsely in follicles and perifollicular areas, some were heavily crowded in particular germinal centres (GCs), suggesting the presence of oligoclonal proliferations of B-cells in GCs. Forty-eight out of 100 B-MLs reacted with anti-idiotype antibodies. This proportion was significantly higher than those reported in Western cases (27-36%), indicating that Japanese B-MLs share public idiotypes much frequently than western cases. The idiotypes demonstrated in these lymphomas, in contrast to those not expressed in any B-ML, were found much commonly in non-tumour lymphocytes, suggesting that such public idiotypes as were common in B-MLs were frequently shared by normal B-lymphocytes. [ABSTRACT FROM AUTHOR]

Two mouse hybridoma antibodies, G6 and H1, with specificity for idiotypic determinants on the heavy chain of human IgM-RF have been produced. Idiotopes recognized by G6 and H1 were expressed on 5/12 and 2/12 RF paraproteins from the Wa idiotype group respectively, but not on paraproteins lacking rheumatoid factor (RF) activity. Inhibition experiments demonstrated that G6 and H1-specific epitopes were located on (or close to) the antibody binding site of RFs, and measurable on the heavy chain but not their light chains. However, it was concluded that the quaternary structure of the antibody-binding site was important for the optimal expression of both idiotopes. The idiotope recognized by G6 was also detected on polyclonal RFs in unfractionated sera from 8/14 patients with rheumatoid arthritis (RA). The results suggest that the G6 idiotope is a highly conserved determinant on the antibody-binding site of RF. These monoclonal antibodies will allow characterization of RF clonality in RA. [ABSTRACT FROM AUTHOR]

The majority of the polyclonal plasma cells identified in the synovial tissues of rheumatoid arthritis patients contain immunoglobulins that express a common idiotype related to that of the monoclonal cryoglobulins of the Wa group (RCRI). In these same tissues, there are twice as many plasma cells which are marked by a common idiotype yet do not show binding of aggregated IgG. These plasma cells are members of an idiotypically parallel set relative to those which produce rheumatoid factor. Direct comparison of rabbit polyclonal RCRI plasma cells with murine monoclonal RCRI plasma cells using two color fluorescent counterstains shows that the epitope recognized by the monoclonal anti-RCRI exists among a set of epitopes present in the RCRI. Since all the monoclonal RCRI plasma cells are not also positive with the polyclonal anti-RCRI antisera, the epitope characterized by the monoclonal antibody Glo 86.3 is not included among the set of epitopes the polyclonal antiserum identifies. A suitably absorbed anti-idiotypic polyclonal antiserum is superior to monoclonal antibodies for the purpose of detection of molecules (and cells) that are part of a polyclonal reaction involved in a given immune response. [ABSTRACT FROM AUTHOR]

The protective anti- B. abortus monoclonal antibody ISS/32 (Ab1) was used as an immunogen to induce anti-idiotypic antibodies (Ab2) in rabbits. The purpose was to produce and characterize anti-idiotypic antibodies that share conformational similarity with the corresponding bacterial epitope recognized by Ab1. The rabbit anti-IdAb so induced was isolated and affinity-purified. Its specificity for the paratope of Ab1 was determined by evaluating its ability to compete with B. abortus for binding to Ab1 in a competitive ELISA assay. The anti-idiotypic ISS/32 antibodies were able to compete with B. abortus for binding to Ab1 in a dose-dependent manner. Hence, the data indicated that the rabbit anti-Id ISS/32 antibodies reacted with or near the antigen-binding site of Ab1. [ABSTRACT FROM AUTHOR]

The immune response of A/J mice against p-azophenylarsonate (Ars)—keyhole limpet hemocyanln(KLH) is characterized by the dominance, late in primary and during the secondary, of a recurrent Idiotype called CRI, encoded by a canonical combination of Ig gene segments. In this study, A/J mice were given Ars coupled to deaggregated human gamma globulins (dHGG) within 24 h after delivery. The offsprings from these mice were then exposed as adults to Ars—KLH. These animals developed an unusual immune response. The level of anti-Ars antibodies was nearly normal but a dramatic shift In repertoire was observed: the cross-reactive idiotype which is the hallmark of the anti-Ars response in A/J mice was completely absent. The idiotype could be recovered by injection of anti-idiotypic antibodies alone, with no need of llpopolysaccharlde coupling. Therefore the presence of antigen at birth can lead to a strong perturbation of idiotype selection. Similar results were obtained with neonatal treatment using antl-IgM antibodies. After recovery of suppression, A/J mice can mount an anti-arsonate response of normal level but devoid of the dominant idiotype. [ABSTRACT FROM PUBLISHER]