An HLA-associated nonresponsiveness to melittin: A components of bee venom+

Lympany, Penny; Kemeny, David M.; Welsh, Ken I.; Lee, T. H.

doi:10.1016/s0091-6749(05)80061-2

Cited by 38 publications

(22 citation statements)

References 36 publications

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“…This view may be useful to address the basis of genetic linkage between disease and HLA typing. In bee allergic patients, HLA-DR7 was found in higher frequency than in control population (43), while it was the opposite for DR4 (44). Interestingly, we found that peptides P13-30, P17-34, P21-38, and P45-62 bind with good efficiency exclusively to the 701 allele.…”

Section: Discussionmentioning

confidence: 58%

HLA-DR Restricted Peptide Candidates for Bee Venom Immunotherapy

Texier

Pouvelle

Busson

et al. 2000

The Journal of Immunology

125

155

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T cell epitopes containing peptides have been recently proposed as an alternative to conventional immunotherapy of allergic diseases because they are expected to be better tolerated than allergen extracts. A principal limitation to their clinical use is that they present an important diversity, which primarily results from the polymorphism of HLA class II molecules. In Caucasian populations, however, seven alleles of the most expressed molecules (namely DRB1*0101, DRB1*0301, DRB1*0401, DRB1*0701, DRB1*1101, DRB1*1301, and DRB1*1501) predominate. Peptides from allergens that would efficiently bind to them should be potential candidates for specific immunotherapy. In this paper, we have determined the peptides present in the major bee venom allergen by investigating the capacity of synthetic peptides that encompass its whole sequence to bind to each allele. Several efficient binders have been identified and are either allele-specific or common to several HLA-DR molecules. Interestingly enough, the 81–97 sequence is universal in the sense that it binds to all studied molecules. This sequence is surrounded by several active regions, which make the 76–106 sequence particularly rich of binding determinants and a good candidate for specific immunotherapy. Statistical analyses of the binding data also provide an overview of the preponderant HLA-DR alleles specificity.

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Section: Discussionmentioning

confidence: 58%

HLA-DR Restricted Peptide Candidates for Bee Venom Immunotherapy

Texier

Pouvelle

Busson

et al. 2000

The Journal of Immunology

125

155

View full text Add to dashboard Cite

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“…Many other possible positive [35, 36, 37, 38, 39] and negative [40, 41, 42] MHC associations with allergen reactivity have been described. The overall effect of the MHC on allergens seems to be a multiplicity of small effects, usually conferring a relative risk of less than 2 [43].…”

Section: Genes Influencing Specific Ige Responses To Particular Allementioning

confidence: 99%

Gene Identification in Asthma and Allergy

Moffatt¹,

Cookson²

1998

Int Arch Allergy Immunol

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Asthma and atopy are due to the interaction between genetic and environmental factors. The genetic basis of asthma and atopy is becoming more certain, with the promise of improvements in the diagnosis and treatment of these disorders. A combination of candidate gene and positional cloning studies has already identified several genes which influence allergic disease. These genes predispose in general to atopy, or influence the specific IgE response to individual allergens, or enhance inflammation independently of atopic mechanisms. In addition to these known factors, the chromosomal localisation of other putative genes is becoming clear.

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“…Contrary to the Th cell epitope specificity, MHC class I1 molecules seem to play a role in determining the type of response. In particular, the expression of the HLA-DR4 haplotype has been associated with the development of nonallergic Ab responses to PLA [42]. In vivo, the processed antigens have to complete with other self or irrelevant peptides for binding to MHC class I1 molecules to be presented to Th cells.…”

Section: Pla45-62mentioning

confidence: 99%

The intensity of T cell receptor engagement determines the cytokine pattern of human allergen‐specific T helper cells

Carballido¹,

Faith²,

Carballido‐Perrig³

et al. 1997

Eur J Immunol

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Enhanced production of T helper (Th)2 cytokines by allergen-specific Th cells plays a major role in the induction and maintenance of IgE-mediated allergic disorders. The mechanism that triggers this type of response in atopic individuals is not fully understood. Allergen-specific human Th cell clones produce interleukin (IL)-4 and low or undetectable levels of interferon (IFN)-gamma after stimulation with low concentrations of antigen. However, these Th cell clones are capable of generating significant amounts of IFN-gamma after optimal activation through their T cell receptor (TcR). Allergen-specific Th cell clones isolated from allergic individuals required higher doses of antigen to reach the plateau of proliferation and to generate Th0 cytokine responses than their counterparts isolated from nonallergic subjects. On the other hand, if allergen was replaced by anti-CD3 monoclonal antibody (mAb), both allergic and nonallergic Th cell clones attained the highest level of proliferation and significant IFN-gamma production in response to equivalent concentrations of anti-CD3 mAb. These results indicate that the strength of T cell ligation, which can be modulated by the availability of the TcR ligand, controls the balance of Thl/Th2 cytokines produced by memory Th cells in vitro. In the particular case of bee venom phospholipase A2, it is shown that the expression of allergen-specific surface Ig on antigen-presenting B cells has little influence on antigen uptake and therefore in determining the levels of T cell activation and cytokine production. Alternatively, the affinity of particular major histocompatibility complex class II molecules on antigen-presenting cells for allergen-derived peptides might determine the amount of specific ligand presented to the Th cells and play a decisive role skewing the Th cell cytokine production towards Th1 or Th2 phenotypes. These findings, which are consistent with the changes in cytokine patterns observed following clinical hyposensitization, suggest that polarized human Th2 cell subsets still retain the capacity to modulate their cytokine pattern.

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An HLA-associated nonresponsiveness to melittin: A components of bee venom+

Cited by 38 publications

References 36 publications

HLA-DR Restricted Peptide Candidates for Bee Venom Immunotherapy

HLA-DR Restricted Peptide Candidates for Bee Venom Immunotherapy

Gene Identification in Asthma and Allergy

The intensity of T cell receptor engagement determines the cytokine pattern of human allergen‐specific T helper cells

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