The Experts below are selected from a list of 483 Experts worldwide ranked by ideXlab platform
Flora Peyvandi - One of the best experts on this subject based on the ideXlab platform.
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generation of anti idiotypic antibodies to detect anti spacer antibody Idiotopes in acute thrombotic thrombocytopenic purpura patients
Haematologica, 2019Co-Authors: An Sofie Schelpe, Elien Roose, Berangere S Joly, Inge Pareyn, Ilaria Mancini, Marina Biganzoli, Hans Deckmyn, Jan Voorberg, Rob Fijnheer, Flora PeyvandiAbstract:In autoantibody-mediated autoimmune diseases, autoantibody profiling allows patients to be stratified and links autoantibodies with disease severity and outcome. However, in immune-mediated thrombotic thrombocytopenic purpura (iTTP) patients, stratification according to antibody profiles and their clinical relevance has not been fully explored. We aimed to develop a new type of autoantibody profiling assay for iTTP based on the use of anti-idiotypic antibodies. Anti-idiotypic antibodies against 3 anti-spacer autoantibodies were generated in mice and were used to capture the respective anti-spacer Idiotopes from 151 acute iTTP plasma samples. We next deciphered these anti-spacer idiotope profiles in iTTP patients and investigated whether these limited idiotope profiles could be linked with disease severity. We developed 3 anti-idiotypic antibodies that recognized particular Idiotopes in the anti-spacer autoantibodies II-1, TTP73 or I-9, that are involved in ADAMTS13 binding; 35%, 24% and 42% of patients were positive for antibodies with the II-1, TTP73 and I-9 Idiotopes, respectively. Stratifying patients according to the corresponding 8 anti-spacer idiotope profiles provided a new insight into the anti-spacer II-1, TTP73 and I-9 idiotope profiles in these patients. Finally, these limited idiotope profiles showed no association with disease severity. We successfully developed 3 anti-idiotypic antibodies that allowed us to determine the profiles of the anti-spacer II-1, TTP73 and I-9 Idiotopes in iTTP patients. Increasing the number of patients and/or future development of additional anti-idiotypic antibodies against other anti-ADAMTS13 autoantibodies might allow idiotope profiles of clinical, prognostic value to be identified.
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Generation of anti-idiotypic antibodies to detect anti-spacer antibody Idiotopes in acute thrombotic thrombocytopenic purpura patients
'Ferrata Storti Foundation (Haematologica)', 2018Co-Authors: An Sofie Schelpe, Elien Roose, Berangere S Joly, Inge Pareyn, Ilaria Mancini, Marina Biganzoli, Hans Deckmyn, Jan Voorberg, Rob Fijnheer, Flora PeyvandiAbstract:In autoantibody-mediated autoimmune diseases, autoantibody profiling allows to stratify patients and link autoantibodies with disease severity and outcome. However, in immune-mediated thrombotic thrombocytopenic purpura patients, stratification according to antibody profiles and their clinical relevance has not been fully explored. We aimed at developing a new type of autoantibody profiling assay for immune-mediated thrombotic thrombocytopenic purpura based on the use of anti-idiotypic antibodies. Anti-idiotypic antibodies against 3 anti-spacer autoantibodies were generated in mice and were used to capture the respective anti-spacer Idiotopes from 151 acute immune-mediated thrombotic thrombocytopenic purpura plasma samples. We next deciphered these anti-spacer idiotope profiles in immune-mediated thrombotic thrombocytopenic purpura patients and investigated if these limited idiotope profiles could be linked with disease severity. We developed 3 anti-idiotypic antibodies that recognized particular Idiotopes in the anti-spacer autoantibodies II-1, TTP73 or I-9, that are involved in ADAMTS13 binding. Thirty-five, 24 and 42% of patients were positive for antibodies with the II-1, TTP73 and I-9 Idiotopes, respectively. Stratifying patients according to the corresponding 8 anti-spacer idiotope profiles revealed an until now unknown insight into the anti-spacer II-1, TTP73 and I-9 idiotope profiles in these patients. Finally, these limited idiotope profiles showed no association with disease severity. We successfully developed 3 anti-idiotypic antibodies that allowed us to determine the profiles of the anti-spacer II-1, TTP73 and I-9 Idiotopes in immune-mediated thrombotic thrombocytopenic purpura patients. Increasing the number of patients and/or future development of additional anti-idiotypic antibodies against other anti-ADAMTS13 autoantibodies might allow to identify idiotope profiles of clinical, prognostic value
Elisabeth H Weiss - One of the best experts on this subject based on the ideXlab platform.
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vh related Idiotopes detected by site directed mutagenesis a study induced by the failure to find cd4 anti idiotypic antibodies mimicking the cellular receptor of hiv
Journal of Immunology, 1992Co-Authors: Winfried Weissenhorn, Yinghua Chen, Gert Riethmuller, Ernst Peter Rieber, Elisabeth H WeissAbstract:The function of the CD4 cell surface protein as coreceptor on T helper lymphocytes and as receptor for HIV makes this glycoprotein a prime target for an immune intervention with mAb. A detailed understanding of the structural determinants on the therapeutic CD4 mAb that are involved in Ag binding or are recognized by anti-idiotypic mAb (anti-Id) may be important for designing antibodies with optimal therapeutic efficacy. Seven anti-Id raised against the CD4 mAb M-T310 were selected from a large panel with the intention to obtain CD4 mimicking structures with specificity for HIV gp120. The selected anti-Id did not react with other CD4-specific mAb cross-blocking M-T310. Among these, mAb M-T404, although having the same L chain as M-T310 and a VH region sequence differing only at 14 amino acid positions, was not recognized by the anti-Id. M-T310 H chain complexed with the J558L L chain reacted with all anti-Id, thus demonstrating that the recognized Idiotopes are located within the VH region. To identify the Idiotopes of M-T310 seen by the anti-Id, variants of M-T404 containing one or more of the M-T310-derived substitutions were generated by oligonucleotide-directed mutagenesis. The reactivity pattern of the mutant proteins with the anti-Id demonstrated that the Idiotopes reside within the complementarity determining region (CDR) 2 and CDR3 loops of the VH region. A major idiotope was defined by a single amino acid in CDR2 that was recognized by three anti-Id, whereas the four other anti-Id reacted with determinants of CDR3. Although the performed amino acid substitutions did influence the Id recognition, Ag binding was not significantly affected, suggesting that none of the anti-Id can be considered as a mimicry of the CD4 Ag.
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vh related Idiotopes detected by site directed mutagenesis
Journal of Immunology, 1992Co-Authors: Winfried Weissenhorn, Gert Riethmuller, Ernst Peter Rieber, Y H Cheng, Elisabeth H WeissAbstract:The function of the CD4 cell surface protein as coreceptor on T helper lymphocytes and as receptor for HIV makes this glycoprotein a prime target for an immune intervention with mAb. A detailed understanding of the structural determinants on the therapeutic CD4 mAb that are involved in Ag binding or are recognized by anti-idiotypic mAb (anti-Id) may be important for designing antibodies with optimal therapeutic efficacy. Seven anti-Id raised against the CD4 mAb M-T310 were selected from a large panel with the intention to obtain CD4 mimicking structures with specificity foHr IV gp120. The selected anti-Id did not reacwt ith other CDCspecific mAb cross-blocking M-T310. Among these, mAb MT404, although having the same L chain as M-T310 and a VH region sequence differing onlya t 14 amino acid positions, was not recognized by the anti-Id. MT310 H chain complexed with the J558L L chain reacted with all anti-Id, thus demonstrating that the recognized Idiotopes are located within the VH region. To identify the Idiotopes of M-T310 seen by the anti-Id, variants of M-T404 containing one or more of the M-T3 1 O-derived substitutions were generated by oligonucleotide-directed mutagenesis. The reactivity pattern of the mutant proteins with the anti-Id demonstrated that the Idiotopes reside within the complementarity determining region (CDR) 2 and CDR3 loops of the VH region. A major idiotope was definebdy a single amino acid in CDR2 that was recognized by three anti-Id, whereas the four other anti-Id reacted with determinants of CDR3. Although the performed amino acid substitutions did influence the Id recognition, Ag binding was not significantly affected, suggesting that none of the anti-Id can be considered as a mimicry of the CD4 Ag
An Sofie Schelpe - One of the best experts on this subject based on the ideXlab platform.
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generation of anti idiotypic antibodies to detect anti spacer antibody Idiotopes in acute thrombotic thrombocytopenic purpura patients
Haematologica, 2019Co-Authors: An Sofie Schelpe, Elien Roose, Berangere S Joly, Inge Pareyn, Ilaria Mancini, Marina Biganzoli, Hans Deckmyn, Jan Voorberg, Rob Fijnheer, Flora PeyvandiAbstract:In autoantibody-mediated autoimmune diseases, autoantibody profiling allows patients to be stratified and links autoantibodies with disease severity and outcome. However, in immune-mediated thrombotic thrombocytopenic purpura (iTTP) patients, stratification according to antibody profiles and their clinical relevance has not been fully explored. We aimed to develop a new type of autoantibody profiling assay for iTTP based on the use of anti-idiotypic antibodies. Anti-idiotypic antibodies against 3 anti-spacer autoantibodies were generated in mice and were used to capture the respective anti-spacer Idiotopes from 151 acute iTTP plasma samples. We next deciphered these anti-spacer idiotope profiles in iTTP patients and investigated whether these limited idiotope profiles could be linked with disease severity. We developed 3 anti-idiotypic antibodies that recognized particular Idiotopes in the anti-spacer autoantibodies II-1, TTP73 or I-9, that are involved in ADAMTS13 binding; 35%, 24% and 42% of patients were positive for antibodies with the II-1, TTP73 and I-9 Idiotopes, respectively. Stratifying patients according to the corresponding 8 anti-spacer idiotope profiles provided a new insight into the anti-spacer II-1, TTP73 and I-9 idiotope profiles in these patients. Finally, these limited idiotope profiles showed no association with disease severity. We successfully developed 3 anti-idiotypic antibodies that allowed us to determine the profiles of the anti-spacer II-1, TTP73 and I-9 Idiotopes in iTTP patients. Increasing the number of patients and/or future development of additional anti-idiotypic antibodies against other anti-ADAMTS13 autoantibodies might allow idiotope profiles of clinical, prognostic value to be identified.
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Generation of anti-idiotypic antibodies to detect anti-spacer antibody Idiotopes in acute thrombotic thrombocytopenic purpura patients
'Ferrata Storti Foundation (Haematologica)', 2018Co-Authors: An Sofie Schelpe, Elien Roose, Berangere S Joly, Inge Pareyn, Ilaria Mancini, Marina Biganzoli, Hans Deckmyn, Jan Voorberg, Rob Fijnheer, Flora PeyvandiAbstract:In autoantibody-mediated autoimmune diseases, autoantibody profiling allows to stratify patients and link autoantibodies with disease severity and outcome. However, in immune-mediated thrombotic thrombocytopenic purpura patients, stratification according to antibody profiles and their clinical relevance has not been fully explored. We aimed at developing a new type of autoantibody profiling assay for immune-mediated thrombotic thrombocytopenic purpura based on the use of anti-idiotypic antibodies. Anti-idiotypic antibodies against 3 anti-spacer autoantibodies were generated in mice and were used to capture the respective anti-spacer Idiotopes from 151 acute immune-mediated thrombotic thrombocytopenic purpura plasma samples. We next deciphered these anti-spacer idiotope profiles in immune-mediated thrombotic thrombocytopenic purpura patients and investigated if these limited idiotope profiles could be linked with disease severity. We developed 3 anti-idiotypic antibodies that recognized particular Idiotopes in the anti-spacer autoantibodies II-1, TTP73 or I-9, that are involved in ADAMTS13 binding. Thirty-five, 24 and 42% of patients were positive for antibodies with the II-1, TTP73 and I-9 Idiotopes, respectively. Stratifying patients according to the corresponding 8 anti-spacer idiotope profiles revealed an until now unknown insight into the anti-spacer II-1, TTP73 and I-9 idiotope profiles in these patients. Finally, these limited idiotope profiles showed no association with disease severity. We successfully developed 3 anti-idiotypic antibodies that allowed us to determine the profiles of the anti-spacer II-1, TTP73 and I-9 Idiotopes in immune-mediated thrombotic thrombocytopenic purpura patients. Increasing the number of patients and/or future development of additional anti-idiotypic antibodies against other anti-ADAMTS13 autoantibodies might allow to identify idiotope profiles of clinical, prognostic value
Constantin A. Bona - One of the best experts on this subject based on the ideXlab platform.
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IMMUNOCHEMICAL AND MOLECULAR CHARACTERIZATION OF REGULATORY Idiotopes EXPRESSED BY MONOCLONAL ANTIBODIES EXHIBITING OR LACKING /32-6 FRUCTOSAN BINDING ACTIVITY
2013Co-Authors: Carol Victor-kobrin, F. A. Bonilla, Blanche Bellon, Constantin A. BonaAbstract:Idiotopes play an important role in idiotype-driven events in an autologous system (1, 2). Regulatory Idiotopes are defined by three criteria: the ability to function as autoimmunogens, the potential to become dominantly expressed because they are recognized by regulatory T cells, and their shared expression by antibodies with different antigenic specificities (3). The regulatory idiotope concept originated from an immunochemical analysis of four members of an idiotypic network pathway initiated by ABPC-48 (A48), a monoclonal protein with/32-6 fructosan binding activity. By studying polyclonal populations of syngeneic Ab2 (anti-Id), Ab3 [anti(anti-Id)], and Ab4 (anti[anti(anti-Id)]) antibodies, we found that Ab3 antibodies share A48 Idiotopes because Ab2 and Ab4 bind to both A48 and Ab ~ antibodies (1). To explain these results, we proposed that Abl antibodies bear a special set of Idiotopes which are immunogenic in an autologous system and which elicit the production of Abe. Parenteral administration of these Ab2 antibodies would lead to the activation of Ab ~ clones that express mainly these regulatory Idiotopes. Hence, the immunization wit
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idiotypes structure and immunogenicity
The FASEB Journal, 1993Co-Authors: Neil S. Greenspan, Constantin A. BonaAbstract:Idiotopes are markers on the variable domains of antigen-specific immunological receptors recognized by anti-idiotypic antibodies or T cells. Therefore, a given antibody or T cell receptor can be identified on the basis of a characteristic idiotypic pattern. The structural correlates for Idiotopes on antibodies have been studied by competitive binding assays, electron microscopy, site-directed mutagenesis, and X-ray crystallography. Immunoglobulin Idiotopes, recognized by antiidiotypic antibodies, can involve amino acid residues from several hypervariable or framework regions and from either or both of the heavy and light chain variable domains. Recent studies suggest that it may be possible to exploit structural knowledge of Idiotopes and anti-Idiotopes for the design of new ligands for immunological or other cell surface receptors. In one instance, it has been possible to use the inferred structural features of an anti-idiotope, which mimics a viral protein, to design a small organic molecule with functional properties approximating those of the antigen and the native anti-idiotope. An alternative strategy being explored for creating new vaccines or therapeutic agents involves engineering an amino acid sequence, corresponding to a segment of a selected nominal antigen, into an immunoglobulin variable domain.
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induction of antibodies to the envelope protein of the human immunodeficiency virus by immunization with monoclonal anti idiotypes
Proceedings of the National Academy of Sciences of the United States of America, 1991Co-Authors: Habib Zaghouani, Daniel J Goldstein, Himanshu Shah, Stephanie Anderson, Martial Lacroix, Gervais Dionne, Ronald Kennedy, Constantin A. BonaAbstract:Abstract Anti-idiotypes that possess the internal image of antigen can induce protective humoral immunity toward microbes. Herein we demonstrate antigen mimicry by monoclonal anti-idiotypes of a distinct epitope of the human immunodeficiency virus (HIV) envelope protein that is defined by a synthetic peptide. This peptide, corresponding to amino acid residues 503-535 (peptide 503-535) of HIV-1 IIIB gp160, induced antibodies in three mammalian species that interacted with HIV-1 gp120 and inhibited in vitro syncytium formation caused by HIV-1, IIIB and MN isolates. Three monoclonal anti-idiotypes were generated against rabbit anti-gp120 antibodies specific for peptide 503-535. These anti-idiotypes recognize an interspecies cross-reactive idiotype expressed on mouse, chimpanzee, baboon, rabbit, and human anti-gp120 antibodies specific for peptide 503-535. The interaction with the cross-reactive idiotype is inhibited by synthetic peptide and HIV-1 gp160. Furthermore, rabbits immunized with the monoclonal anti-idiotypes produced antibodies that also bind HIV-1 gp120 and gp160 and recognized the epitope defined by peptide 503-535.
Winfried Weissenhorn - One of the best experts on this subject based on the ideXlab platform.
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vh related Idiotopes detected by site directed mutagenesis a study induced by the failure to find cd4 anti idiotypic antibodies mimicking the cellular receptor of hiv
Journal of Immunology, 1992Co-Authors: Winfried Weissenhorn, Yinghua Chen, Gert Riethmuller, Ernst Peter Rieber, Elisabeth H WeissAbstract:The function of the CD4 cell surface protein as coreceptor on T helper lymphocytes and as receptor for HIV makes this glycoprotein a prime target for an immune intervention with mAb. A detailed understanding of the structural determinants on the therapeutic CD4 mAb that are involved in Ag binding or are recognized by anti-idiotypic mAb (anti-Id) may be important for designing antibodies with optimal therapeutic efficacy. Seven anti-Id raised against the CD4 mAb M-T310 were selected from a large panel with the intention to obtain CD4 mimicking structures with specificity for HIV gp120. The selected anti-Id did not react with other CD4-specific mAb cross-blocking M-T310. Among these, mAb M-T404, although having the same L chain as M-T310 and a VH region sequence differing only at 14 amino acid positions, was not recognized by the anti-Id. M-T310 H chain complexed with the J558L L chain reacted with all anti-Id, thus demonstrating that the recognized Idiotopes are located within the VH region. To identify the Idiotopes of M-T310 seen by the anti-Id, variants of M-T404 containing one or more of the M-T310-derived substitutions were generated by oligonucleotide-directed mutagenesis. The reactivity pattern of the mutant proteins with the anti-Id demonstrated that the Idiotopes reside within the complementarity determining region (CDR) 2 and CDR3 loops of the VH region. A major idiotope was defined by a single amino acid in CDR2 that was recognized by three anti-Id, whereas the four other anti-Id reacted with determinants of CDR3. Although the performed amino acid substitutions did influence the Id recognition, Ag binding was not significantly affected, suggesting that none of the anti-Id can be considered as a mimicry of the CD4 Ag.
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vh related Idiotopes detected by site directed mutagenesis
Journal of Immunology, 1992Co-Authors: Winfried Weissenhorn, Gert Riethmuller, Ernst Peter Rieber, Y H Cheng, Elisabeth H WeissAbstract:The function of the CD4 cell surface protein as coreceptor on T helper lymphocytes and as receptor for HIV makes this glycoprotein a prime target for an immune intervention with mAb. A detailed understanding of the structural determinants on the therapeutic CD4 mAb that are involved in Ag binding or are recognized by anti-idiotypic mAb (anti-Id) may be important for designing antibodies with optimal therapeutic efficacy. Seven anti-Id raised against the CD4 mAb M-T310 were selected from a large panel with the intention to obtain CD4 mimicking structures with specificity foHr IV gp120. The selected anti-Id did not reacwt ith other CDCspecific mAb cross-blocking M-T310. Among these, mAb MT404, although having the same L chain as M-T310 and a VH region sequence differing onlya t 14 amino acid positions, was not recognized by the anti-Id. MT310 H chain complexed with the J558L L chain reacted with all anti-Id, thus demonstrating that the recognized Idiotopes are located within the VH region. To identify the Idiotopes of M-T310 seen by the anti-Id, variants of M-T404 containing one or more of the M-T3 1 O-derived substitutions were generated by oligonucleotide-directed mutagenesis. The reactivity pattern of the mutant proteins with the anti-Id demonstrated that the Idiotopes reside within the complementarity determining region (CDR) 2 and CDR3 loops of the VH region. A major idiotope was definebdy a single amino acid in CDR2 that was recognized by three anti-Id, whereas the four other anti-Id reacted with determinants of CDR3. Although the performed amino acid substitutions did influence the Id recognition, Ag binding was not significantly affected, suggesting that none of the anti-Id can be considered as a mimicry of the CD4 Ag
