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Tuomas Virtanen

Publications and source records attributed to Tuomas Virtanen.

8 recordsLinked to original sources
PubMed2006

Prospects for peptide-based immunotherapy for dog allergy.

PURPOSE OF REVIEW: Tolerance to ubiquitous environmental substances, allergens, can be accomplished with specific immunotherapy. Conducting therapy with allergen peptides helps to avoid immediate allergic reactions. Dogs are a source of important indoor allergens, which necessitates the development of effective modes of therapy against the allergy they cause. RECENT FINDINGS: The human T-cell epitopes of the major dog allergen Can f 1 were determined recently. They were found to be distributed in seven epitope regions along the molecule. For the peptide immunotherapy of dog allergy, using a pool of seven peptides, one from each of the epitope regions of Can f 1, seems at present to be the best approach. As Can f 1 is not as immunodominant as the main allergens of some other mammals, it remains to be seen whether peptides from other dog allergens should be included in the pool. SUMMARY: The use of a pool of seven peptides from the T-cell epitope regions of Can f 1 is likely to be feasible for treating dog allergy in a great majority of Caucasian populations. In the future, patient-tailored preparations of variants of the T-cell epitope-containing peptides may offer a way to enhance the efficacy of peptide-based immunotherapy.

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PubMed2005

Immunomodulatory potential of heteroclitic analogs of the dominant T-cell epitope of lipocalin allergen Bos d 2 on specific T cells.

Peptide-based allergen immunotherapy is a novel alternative for conventional allergen immunotherapy. Here, we have characterized the immunomodulatory potential of heteroclitic peptide analogs of the immunodominant epitope of lipocalin allergen Bos d 2 on specific human T-cell clones. The TCR affinity of Bos d 2-specific T-cell clones for the natural peptide ligand and its heteroclitic analogs was assessed with fluorescent-labeled MHC class II tetramers. The activation and cytokine production of the clones were analyzed upon stimulation with the different ligands. Moreover, the capacity of the heteroclitic analogs to induce hyporesponsiveness and cell death was examined. The T-cell clones F1-9 and K3-2 bound MHC class II tetramers loaded with the heteroclitic peptide analogs of the immunodominant epitope of Bos d 2 with increased affinity. At similar peptide concentrations, stimulation of the clones with the heteroclitic analogs favored increased IFN-gamma/IL-4 and IFN-gamma/IL-5 ratios in comparison with stimulation with the natural peptide ligand. Moreover, the T-cell clones stimulated with the heteroclitic analogs exhibited an increased susceptibility to cell death or hyporesponsiveness upon re-stimulation. Our results suggest that heteroclitic analogs of a T-cell epitope of an allergen may enhance the efficacy of peptide-based allergen immunotherapy.

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PubMed2005

T cell epitope-containing peptides of the major dog allergen Can f 1 as candidates for allergen immunotherapy.

One prerequisite for developing peptide-based allergen immunotherapy is knowing the T cell epitopes of an allergen. In this study, human T cell reactivity against the major dog allergen Can f 1 was investigated to determine peptides suitable for immunotherapy. Seven T cell epitope regions (A-G) were found in Can f 1 with specific T cell lines and clones. The localization of the epitope regions shows similarities with those of the epitopes found in Bos d 2 and Rat n 1. On average, individuals recognized three epitopes in Can f 1. Our results suggest that seven 16-mer peptides (p15-30, p33-48, p49-64, p73-88, p107-122, p123-138, and p141-156), each from one of the epitope regions, show widespread T cell reactivity in the population studied, and they bind efficiently to seven HLA-DRB1 molecules (DRB1*0101, DRB1*0301, DRB1*0401, DRB1*0701, DRB1*1101, DRB1*1301, and DRB1*1501) predominant in Caucasian populations. Therefore, these peptides are potential candidates for immunotherapy of dog allergy.

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PubMed2003

The immunodominant epitope of lipocalin allergen Bos d 2 is suboptimal for human T cells.

We have proposed earlier that the poor capacity of the lipocalin allergen Bos d 2 to stimulate highly allergic subjects' peripheral blood mononuclear cells could be ascribed to endogenous lipocalins and could be related to the allergenic potential of the molecule. Here, we have characterized the proliferative and cytokine responses of human T cell clones against the immunodominant epitope of Bos d 2. We observed, for clone F1-9, that a substitution of aspartic acid for asparagine in the core region of the epitope increased the stimulatory capacity of the peptide about 100-fold in comparison with the natural peptide. For clone K3-2, from a different patient, the substitution of lysine for glutamine or isoleucine for leucine in the core region resulted in about 30-fold and 10-fold increases in the stimulatory capacity of the peptides, respectively. The clones also recognized self-protein-derived peptides but not the peptides derived from other lipocalins. We suggest that the poor recognition of the immunodominant epitope of Bos d 2 can be a factor accounting for Bos d 2-allergic subjects' weak cellular responses. Suboptimal recognition of self and allergen epitopes by T cells may be of significance for the allergenicity of proteins.

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PubMed2002

Microarrayed allergen molecules: diagnostic gatekeepers for allergy treatment.

Type I allergy is an immunoglobulin E (IgE)-mediated hypersensitivity disease affecting more than 25% of the population. Currently, diagnosis of allergy is performed by provocation testing and IgE serology using allergen extracts. This process defines allergen-containing sources but cannot identify the disease-eliciting allergenic molecules. We have applied microarray technology to develop a miniaturized allergy test containing 94 purified allergen molecules that represent the most common allergen sources. The allergen microarray allows the determination and monitoring of allergic patients' IgE reactivity profiles to large numbers of disease-causing allergens by using single measurements and minute amounts of serum. This method may change established practice in allergy diagnosis, prevention, and therapy. In addition, microarrayed antigens may be applied to the diagnosis of autoimmune and infectious diseases.

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PubMed2002

Lipocalin allergen Bos d 2 is a weak immunogen.

The immunological characteristics of an important group of animal-derived allergens, lipocalins, are poorly known. To explore the immunology of the lipocalin allergen Bos d 2, several mouse strains with different H-2 haplotypes were immunized with the allergen. Only the BALB/c mouse mounted a distinct humoral response against Bos d 2. The proliferative spleen cell responses of all mouse strains remained very weak. Further experiments with BALB/c mice confirmed that Bos d 2 is a weak inducer of both humoral and cellular responses, and that the responses were weaker than with the control antigens hen egg lysozyme (HEL) and tetanus toxoid. IgG subclass analyses showed that Bos d 2 was prone to favor the T(h)2 response. Although s.c. immunization using complete Freund's adjuvant favored the T(h)1-deviated immune response by lymph node cells, Bos d 2 was able to induce the production of IL-4 while the control antigen HEL did not. Epitope mapping revealed that BALB/c mice recognized one immunodominant epitope in Bos d 2, almost identical to that recognized by humans. The epitope was shown to be immunogenic in subsequent experiments. However, further studies are needed to clarify the significance of priming and stimulation doses of the immunodominant and other epitopes in Bos d 2 for the outcome of immune response against the allergen. The murine immune response against Bos d 2 closely resembled that observed in humans. The weak immunogenicity of Bos d 2 may be associated with its allergenicity.

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