Implications of the presence of an internal image of the antigen in anti-idiotypic antibodies: Possible application to vaccine production

Nisonoff, Alfred; Lamoyi, Edmundo

doi:10.1016/0090-1229(81)90228-2

Cited by 289 publications

(110 citation statements)

References 16 publications

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“…28 and 29) and the apparent production of idiotype-positive antibodies by animals that are lacking the presumed variable region gene required for idiotype expression (30). One explanation for these phenomena may be that polyclonal anti-idiotypic antibodies against conformation-dependent determinants on immunoglobulins often contain a minor component with the "internal image" of the antigen (31)(32)(33)(34) Additionally, monoclonal anti-idiotope reagents may crossreact with substances that share a conformational determinant with idiotype-positive immunoglobulins in spite of a distinct primary structure (36,37). By comparison, the HVPinduced anti-idiotypic antibody is free of internal image components and may crossreact with substances that include a region of similar primary structure.…”

Section: Discussionmentioning

confidence: 99%

Anti-hypervariable region antibody induced by a defined peptide: an approach for studying the structural correlates of idiotypes.

Chen¹,

Houghten²,

Fong³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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The structural correlates of idiotypes have been sought in several antibody systems. However, the precise molecular basis of idiotypes are exceedingly difficult to define.Antibodies of predetermined specificity can be induced by immunization with synthetic peptides. In the present experiments, a synthetic peptide corresponding to a hypervariable region on a monoclonal human IgM rheumatoid factor (Sie) has been used to induce specific anti-hypervariable region antibodies. The antibodies bound to the intact Ig molecule and to its isolated heavy chains but not to other IgM paraproteins nor to pooled human IgG. The binding of the antibody to the intact IgM was inhibited specifically by the free peptide, and the antibody activity was removed by a peptide-coupled affrmity column. These results clearly demonstrate that specific antiidiotypic antibody of predefined specificity can be induced by a hypervariable region peptide. Antibodies of this class may provide a new tool for defining the structural correlates of idiotypes.The study of idiotypes (1) has greatly advanced our understanding of immunoglobulin genetics and antibody structure (2, 3). In addition, idiotypes have been postulated to play an essential role in the generation and regulation of diverse immune responses (4-6).The structural correlates of idiotypes have been sought in several well-defined antibody systems (7)(8)(9)(10)(11)(12). Because of the common occurrence of monoclonal human IgM paraproteins with anti-IgG activity (rheumatoid factors), the idiotypes and the primary amino acid sequences of these proteins were compared in detail (9, 10, 13). The heavy and light chains from two monoclonal IgM rheumatoid factors (IgM-RF) with crossreactive idiotypes (e.g., Lay and Pom) had identical amino acid sequences in three of six complementarity-determining regions but differed substantially in the framework regions (9, 10). These results suggested that the hypervariable regions of the heavy and light chains were the structural correlates of idiotypic determinants. Similar comparisons of amino acid sequences and idiotypes among mouse monoclonal antibodies with antigen binding activity have yielded much the same conclusions (8,11,12). Noticeably, in the murine anti-Dextran system, one private idiotype and one public idiotype were assigned, respectively, to the third and the second hypervariable region of the heavy chain (11). However, in most other cases, it has proven to be extremely difficult to associate a particular idiotypic determinant with a specific amino acid sequence (7 MATERIALS AND METHODSPreparation of Synthetic Peptide. Peptides were prepared by the solid-phase method (17-20), using a Beckman model 990B peptide synthesizer. Briefly, 1.00 g (ca. 0.5 milliequivalent) of N-t-butoxycarbonylglutamic acid (BocGlu) resin was used along with the following side-chain protecting groups: O-bromobenzyloxycarbonyl for tyrosine and lysine; O-benzyl for glutamic acid and aspartic acid; S-methoxybenzyl for cysteine. Protected amino acids were recrystalli...

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Section: Discussionmentioning

confidence: 99%

Anti-hypervariable region antibody induced by a defined peptide: an approach for studying the structural correlates of idiotypes.

Chen¹,

Houghten²,

Fong³

et al. 1984

Proc. Natl. Acad. Sci. U.S.A.

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“…Manipulation of the immune response by injection of antibodies to idiotypes has been used in several systems (28)(29)(30)(31). In these studies exposure to antigen after the injection of antiidiotypic reagents resulted in either suppression of the idiotype-bearing antigen-binding molecule or increased idiotype expression and antigen-binding activity, depending upon the route of injection.…”

Section: Effect Of Dose Of Antiidiotype On the Magnitude Of The Dth Rmentioning

confidence: 99%

Syngeneic monoclonal antiidiotype can induce cellular immunity to reovirus.

Sharpe¹,

Gaulton²,

McDADE³

et al. 1984

The Journal of Experimental Medicine

134

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Viruses attach to cells via specialized attachment proteins that interact with specific cell surface receptors (1-5). An understanding of such virus-host cell interactions may provide new insights into the pathogenesis and prevention of infectious diseases (6).The mammalian reoviruses, segmented, double-stranded RNA viruses include three serotypes (7). The segmented nature of the reovirus genome has permitted a genetic approach for the identification of the role of individual viral components in pathogenesis, making the study of virus-host interactions more amenable to direct experimentation (8). These studies have revealed that each of the three outer capsid proteins (#lc, ~1, ~r3) plays critical, distinct roles in viral virulence. One of the outer capsid proteins, al, the reovirus hemagglutinin (HA), ~ has been shown to be the reovirus cell attachment protein (9-12). Studies utilizing monoclonal antibodies have revealed that the HA is divided into three distinct domains (13, 14), one of which governs the important biologic properties of receptor interaction, recognition by cytotoxic T lymphocytes (CTL) and recognition by neutralizing antibody (15,17). Reovirus mutants at this site, selected for resistance to neutralization, are altered in cell tropism (in the nervous system) (16) and in recognition by CTL (17). Therefore, monoclonal antibodies directed to this site, block a number of important biologic properties of reovirus.That such diverse biologic properties as CTL recognition and viral neutralization localize to one part of the HA suggests that binding is restricted by a unique conformation or, alternatively, by a set of epitopes on the HA. This implies that the receptor for virus on immune CTL, the natural receptor found on neurons, and the binding moiety of neutralizing monoclonal antibodies (idiotype) share a common configuration as well.To test this possibility, syngeneic monoclonal antibodies were raised against the idiotype portion of a prototypic neutralizing monocional antibody, 9BG5 (18,19). The antiidiotype obtained has been shown to block both viral binding

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“…13 The results suggested that the anti-Id antibodies bore an internal image of flagellar antigens of C. chauvoei.…”

Section: Discussionmentioning

confidence: 89%

Antigenic mimicry of Clostridium chauvoei flagella by polyclonal anti-idiotypic antibodies

Kijima-Tanaka

Tsutsumi²,

Suzuki³

et al. 1994

Journal of Medical Microbiology

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Summary. Polyclonal rabbit anti-idiotypic (anti-Id) antibodies against two monoclonal antibodies (MAbs) specific for the flagella of Clostridiurn chauvoei were produced, purified and characterised. Lack of cross-reactivity with heterologous MAbs indicated that the anti-Id antibodies were highly specific. The surface-exposed epitopes of the flagellar filament recognised with protective MAb were further distinguished by the anti-Id antibodies. Moreover, each anti-Id antibody inhibited the binding of its related MAb to flagellar antigens in a competitive enzyme-linked immunosorbent assay, suggesting that the anti-Id antibodies bore an internal image of the flagellar antigens. The survival rate of mice was increased to nearly twice that of controls by immunisation with anti-Id 41, which had been produced with a protective MAb; in contrast, anti-Id 114, produced with a non-protective MAb, failed to immunise. The results suggest that an anti-Id antibody containing an internal image of C. chauvoei flagella might be used as a vaccine.

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Implications of the presence of an internal image of the antigen in anti-idiotypic antibodies: Possible application to vaccine production

Cited by 289 publications

References 16 publications

Anti-hypervariable region antibody induced by a defined peptide: an approach for studying the structural correlates of idiotypes.

Anti-hypervariable region antibody induced by a defined peptide: an approach for studying the structural correlates of idiotypes.

Syngeneic monoclonal antiidiotype can induce cellular immunity to reovirus.

Antigenic mimicry of Clostridium chauvoei flagella by polyclonal anti-idiotypic antibodies

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