A novel technique to link either proteins or peptides to gammaglobulin to construct tolerogens

Borel, Halina; Borel, Yves

doi:10.1016/0022-1759(90)90146-m

Cited by 14 publications

(14 citation statements)

References 8 publications

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“…Mice tolerized with 1 mg of 12-26-IgG 10 days before peptide challenge had reduced LN IL-2 responses but unaffected PPD recall proliferative responses compared with control P6-injected animals (Fig. 4B) [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] epitope. Because polymerized flagellin is a wellcharacterized T-independent antigen (31), we constructed a 12-26 flagellin fusion protein with a strategy previously described (18).…”

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confidence: 99%

Epitope-specific tolerance induction with an engineered immunoglobulin.

Zambidis

Scott

1996

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

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Isologous and heterologous immunoglobulins have been shown to be extremely effective as tolerogenic carriers for nearly 30 years. The efficacy of these proteins is due in part to their long half-life in vivo, as well as their ability to crosslink surface IgM with Fc receptors. The concept of using IgG as a carrier molecule to induce unresponsiveness in the adult immune system has been exploited for simple haptens, such as nucleosides, as well as for peptides. To further evaluate the in vivo potential of these molecules for inducing tolerance to a defined epitope, we have engineered a fusion protein of mouse IgGl with the immunodominant epitope 12-26 from bacteriophage A cI repressor protein. This 15-mer, which contains both a B-cell and T-cell epitope, has been fused in-frame to the N terminus of a mouse heavy chain IgGl construct, thus creating a "genetic hapten-carrier" system. We describe a novel in vitro and in vivo experimental system for studying the feasibility of engineered tolerogens, consisting of a recombinant flagellin challenge antigen and a murine IgGl tolerogen, both expressing the A repressor epitope 12-26. Herein, we show that peptide-grafted IgG molecules injected i.v., or expressed by transfected, autologous B cells, can efficiently modulate the cellular and humoral immune responses to immunodominant epitopes. This model displays the feasibility of "tailor-designing" immune responses to whole antigens by selecting epitopes for either tolerance or immunity.

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confidence: 99%

Epitope-specific tolerance induction with an engineered immunoglobulin.

Zambidis

Scott

1996

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

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“…This has been supported by the observation that haptens linked to isologous gammaglobuline can induce unresponsiveness [2,3], made possible by the development of a novel tech nique which links soluble protein It) IgG [4], We propose to induce immunologic tolerance by a tolerogen which suppresses immunity.…”

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confidence: 76%

Administration of a Tolerogen to Prevent Allergy

Borel¹,

Fritsché²

1992

Int Arch Allergy Immunol

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A novel strategy to prevent an allergic immune response is presented. We tested the idea that a potent allergen such as cow’s milk Beta lactoglobuline (βLG) can be rendered tolerogenic by covalent linkage to isologous gammaglobuline. We found that, under certain conditions, a single intravenous dose (of 2 mg) of βLG conjugated to rat gammaglobuline prevent both IgE and IgG antibodies to βLG. This was allergen specific. It appears to be also effective in sensitized animals. In addition, it prevents serotonine release by rat mastocytes both in vivo and in vitro. We suggest that this approach could provide a novel strategy to specifically prevent allergy.

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“…Administration of tolerogen appears to suppress both T and B cell immune responses, suggesting that unresponsiveness rather than immunity was induced. It has to be stressed that for our conjugates to be tolerogenic, a number of conditions have to be fulfilled [7,8]. Two are critical: the degree of sub stitution of allergen linked to IgG and the monomeric nature of the conjugate.…”

Section: Discussionmentioning

confidence: 99%

“…The advantages of OVA as a model allergen are not only that the structure of the molecule and the amino acid se quence are well known but also that the individual allergen ic epitopes are well characterized [13,14], Peptides linked to IgG [7] provide a means of determining whether allergenic and tolerogenic peptides are the same. It is our hope that the ability to present allergens as tolerogens through conjuga tion with IgG will not only define the significance of al lergic epitopes for tolerance induction but will also provide a new strategic approach for specific allergy prevention.…”

Section: Discussionmentioning

confidence: 99%

“…Protein-immunoglobulin conjugates were made as previously de scribed using disuccinimidyl suberate (DSS) to link covalently cither (5-lactoglobulin (BLG) or ovalbumin (OVA) to rat immunoglobulin [7,8], Following chromatography on sephacryl (S300), only the fractions corresponding to monomeric IgG were used to induce unresponsive ness. The experimental protocol was as previously describet [8J.…”

Section: Methodsmentioning

confidence: 99%

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Food Allergens Transformed into Tolerogens

Borel¹,

Fritsché²,

Borel³

et al. 1995

Int Arch Allergy Immunol

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Antigen presentation determines immunologic outcome, and by modifying the presentation of allergen to the host one can prevent an allergic response. Under certain conditions, covalent linkage, of ovalbumin to rat IgG, a molecule already tolerated by the host, can make a protein-IgG conjugate which down-regulates the immune response to this food allergen. The suppression is allergen specific. It affects both T and B cell immune responses. Administration of allergens linked to isologous IgG may provide a novel strategy for allergy prevention.

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A novel technique to link either proteins or peptides to gammaglobulin to construct tolerogens

Cited by 14 publications

References 8 publications

Epitope-specific tolerance induction with an engineered immunoglobulin.

Epitope-specific tolerance induction with an engineered immunoglobulin.

Administration of a Tolerogen to Prevent Allergy

Food Allergens Transformed into Tolerogens

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