Induction of non-responsiveness in human allergen-specific type 2 T helper cells

Yssel, Hans; Fasler, Stephan; Lamb, Jonathan R.; Vries, J E de

doi:10.1016/0952-7915(94)90003-5

Cited by 49 publications

(17 citation statements)

References 42 publications

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“…Vaccination with nonanaphylactic allergen derivatives or peptides which target allergenspecific T helper cells might lead to disease improvement by (a) induction of tolerance in allergen-specific T cells (39)(40)(41); (b) induction of anergy (42,43); (c) perhaps even the switching of allergen-specific TH2 clones into TH1-like clones which may then display a reduced and/or altered cytokine expression (44); or (d) induction of blocking antibodies which are able to recognize the unfolded fragments as well as natural Bet v 1 as exemplified by the mouse monoclonal antibody 14 (21). Although induction of T cell tolerance against a specific antigen has been demonstrated by injecting a single T cell epitope derived thereof (45,46), the present approach comprises all known relevant Bet v 1 T cell epitopes.…”

Section: Discussionmentioning

confidence: 99%

Conversion of the major birch pollen allergen, Bet v 1, into two nonanaphylactic T cell epitope-containing fragments: candidates for a novel form of specific immunotherapy.

Vrtala¹,

Hirtenlehner²,

Vangelista³

et al. 1997

J. Clin. Invest.

199

230

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Section: Discussionmentioning

confidence: 99%

Conversion of the major birch pollen allergen, Bet v 1, into two nonanaphylactic T cell epitope-containing fragments: candidates for a novel form of specific immunotherapy.

Vrtala¹,

Hirtenlehner²,

Vangelista³

et al. 1997

J. Clin. Invest.

199

230

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“…It could be shown that human T-cells become nonresponsive when antigen presentation occurs in the absence of costimulatory signals (34). Furthermore, mice administered peptides that represented major T-cell epitopes of allergens became tolerant of the complete allergen (35,36), and the first clinical studies are underway to determine whether peptide immunotherapy may represent a low-risk alternative to traditional immunotherapy (90).…”

Section: Nonanaphylactic Derivatives Of Allergens For Specific Activementioning

confidence: 99%

“…T-cell epitopes are usually not recognized by IgE antibodies, a fact which has made it an attractive idea to use nonanaphylactic T-cellepitope-containing allergen modifications, allergen fragments, or synthetic peptides for specific immunotherapy (32,33). While there is ample evidence that T-celi epitopes can induce tolerance, anergy, or immunodeviation in vitro, as well as in experimental animal models (34)(35)(36), clinical studies are required to provide formal proof that T-cellepitope-based immunotherapy can lead to improvement of clinical symptoms.…”

Section: Determination Of B-cell and T-cell Epitopesmentioning

confidence: 99%

Recombinant allergens

Valenta

Vrtala

Laffer

et al. 1998

Allergy

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A great variety of recombinant plant, mite, mold, mammal, and insect allergens have been expressed in heterologous hosts (e.g., Escherichia coli), their cDNA being used as a template. The number of biologically active recombinant allergens available for experimental, diagnostic, and therapeutic purposes is increasing tremendously. Recombinant allergens have proven to be valuable tools to investigate T‐cell and B‐cell recognition of allergens as well as to study mechanisms of specific IgE regulation. The immunologic equivalence of many relevant recombinant allergens with their natural counterparts has been demonstrated, and the three‐dimensional structures of several recombinant allergens have been described recently. As a result of extensive cross‐reactivities among the relevant allergens, it appears that the number of epitopes needed for diagnosis and specific immunotherapy is less diverse than originally anticipated and might be soon covered by recombinant molecules. Recombinant allergens have been used for successful in vitro, as well as in vivo, allergy diagnosis, and work is in progress to produce recombinant allergen derivatives with reduced anaphylactic potential to improve current forms of immunotherapy.

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“…From a similar standpoint, the combination ofDerfl p 18-31 + Der f 1 p206-223 or Der f 1 p75-94 + Der f 1 p206-223 stimulat ed T cells of all 6 subjects listed in figure 1. While the pre cise mechanisms for the in vivo tolerance induction with peptide antigens remain to be determined, human T-T inter-actions with peptide antigens are prone to induce T cell anergy, because human activated T cells express class II HLA molecules [23,24]. Moreover, it may not be necessary to target all the antigen-specific T cells, if bystander sup pression in the microenvironment and/or active suppression by anergic T cells [25] take place.…”

Section: Antigen-presenting Hla Moleculesmentioning

confidence: 99%

<i>Dermatophagoides farinae</i>-1-Derived Peptides and HLA Molecules Recognized by T Cells from Atopic Individuals

Matsuoka

Kohrogi²,

Ando³

et al. 1997

Int Arch Allergy Immunol

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Der f 1, the group I allergen in Dermatophagoides farinae extracts, is a major source of inhalation allergens in Japan. Using the mixture of a panel of overlapping synthetic peptides that spread over the entire Der f 1 molecule, we found that polyclonal Der f 1-specific short-term T cell lines prepared from peripheral blood of 6 individuals allergic to Der f who carry most of the common HLA haplotypes seen in the Japanese population can respond to 16 different peptides. Eight of 16 peptides stimulated T cells of more than 2 donors, regardless of the HLA types. Proliferative responses of four T cell lines were markedly inhibited by mAb HU4 (anti-HLA-DRB1+B5), one was inhibited partially by HU11 (anti-HLA-DQ4+5+6), and one was inhibited fully by a combination of HU4, L243 (anti-HLA-DRB1+B4) and PLM16 (anti-HLA-DRB3) but only partially by each of these mAbs. One of these T cell lines, DT, of which the proliferative response was partially inhibited by HUH, was cloned. Indeed, the T cell clones were restricted by DQ6 molecules on an HLA-DRB1*1501-DRB5*0101-DQA1*0102-DQB1*0602 haplotype. These results indicate that patients’ T cells recognize Der f 1 in association mainly with HLA-DRA/DRB1, but that DQA1/DQB1, DRA/DRB3 and possibly DRA/DRB4 gene products also function as antigen-presenting molecules. Thus, although some peptides have a more potent T cell-stimulatory activity than others, the T cell receptor ligands formed with the Der f 1 molecule are highly heterogeneous.

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Induction of non-responsiveness in human allergen-specific type 2 T helper cells

Cited by 49 publications

References 42 publications

Conversion of the major birch pollen allergen, Bet v 1, into two nonanaphylactic T cell epitope-containing fragments: candidates for a novel form of specific immunotherapy.

Conversion of the major birch pollen allergen, Bet v 1, into two nonanaphylactic T cell epitope-containing fragments: candidates for a novel form of specific immunotherapy.

Recombinant allergens

<i>Dermatophagoides farinae</i>-1-Derived Peptides and HLA Molecules Recognized by T Cells from Atopic Individuals

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