Potential of an altered peptide ligand of lipocalin allergen Bos d 2 for peptide immunotherapy

Kinnunen, Tuure; Jutila, K. L.; Kwok, William W.; Rytkönen‐Nissinen, Marja; Immonen, Anu K.; Saarelainen, Soili; Närvänen, Ale; Taivainen, Antti; Virtanen, Tuomas

doi:10.1016/j.jaci.2007.01.011

Cited by 30 publications

(37 citation statements)

References 40 publications

(49 reference statements)

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“…MHC class II peptide tetramer technology has been recently used succesfully in the field of allergy to characterize allergen-specific CD4 ϩ T cell responses (15)(16)(17). Soluble multimeric tetramers comprise fluorescently labeled recombinant MHC class II molecules, each bound to a high-affinity T cell epitope (18 -21).…”

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confidence: 99%

Assessment of Bet v 1-Specific CD4+ T Cell Responses in Allergic and Nonallergic Individuals Using MHC Class II Peptide Tetramers

Overtvelt

Wambre

Maillère

et al. 2008

The Journal of Immunology

111

118

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In this study, we used HLA-DRB1*0101, DRB1*0401, and DRB1*1501 peptide tetramers combined with cytokine surface capture assays to characterize CD4+ T cell responses against the immunodominant T cell epitope (peptide 141–155) from the major birch pollen allergen Bet v 1, in both healthy and allergic individuals. We could detect Bet v 1-specific T cells in the PBMC of 20 birch pollen allergic patients, but also in 9 of 9 healthy individuals tested. Analysis at a single-cell level revealed that allergen-specific CD4+ T cells from healthy individuals secrete IFN-γ and IL-10 in response to the allergen, whereas cells from allergic patients are bona fide Th2 cells (producing mostly IL-5, some IL-10, but no IFN-γ), as corroborated by patterns of cytokines produced by T cell clones. A fraction of Bet v 1-specific cells isolated from healthy, but not allergic, individuals also expresses CTLA-4, glucocorticoid-induced TNF receptor, and Foxp 3, indicating that they represent regulatory T cells. In this model of seasonal exposure to allergen, we also demonstrate the tremendous dynamics of T cell responses in both allergic and nonallergic individuals during the peak pollen season, with an expansion of Bet v 1-specific precursors from 10−6 to 10−3 among circulating CD4+ T lymphocytes. Allergy vaccines should be designed to recapitulate such naturally protective Th1/regulatory T cell responses observed in healthy individuals.

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mentioning

confidence: 99%

Assessment of Bet v 1-Specific CD4+ T Cell Responses in Allergic and Nonallergic Individuals Using MHC Class II Peptide Tetramers

Overtvelt

Wambre

Maillère

et al. 2008

The Journal of Immunology

111

118

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“…Their application has been reported for T cell epitopes from Lol p 1 (35), Fel d 1 (36), Der p 1 (37), Bos d 2 (20), and Bet v 1 (26,38). Herein, we demonstrate that stable, high-affinity MHC class II tetramers containing HLA-DR1 molecules and Art v 1 19 -36 , a peptide containing the immunodominant epitope, can also be used to identify Art v 1-specific T cells (Figs.…”

Section: Discussionmentioning

confidence: 99%

“…Due to its uniform T cell response, mugwort pollen allergy appears to be an ideal model for the investigation of HLA/peptide-TCR interactions, especially with respect to peptide immunotherapy. The concept of using natural or altered peptide ligands as vaccines has been revived recently as a promising therapeutic approach in allergy and other T cell-mediated diseases (19,20).…”

mentioning

confidence: 99%

Characterization of HLA Class II/Peptide-TCR Interactions of the Immunodominant T Cell Epitope in Art v 1, the Major Mugwort Pollen Allergen

Jahn‐Schmid

Sirven

Leb

et al. 2008

The Journal of Immunology

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More than 95% of mugwort pollen-allergic individuals are sensitized to Art v 1, the major allergen in mugwort pollen. Interestingly, the CD4 T cell response to Art v 1 involves only one single immunodominant peptide, Art v 125–36 (KCIEWEKAQHGA), and is highly associated with the expression of HLA-DR1. Therefore, we investigated the molecular basis of this unusual immunodominance among allergens. Using artificial APC expressing exclusively HLA-DRB1*0101 and HLA-DRA*0101, we formally showed that DR1 acts as restriction element for Art v 125–36-specific T cell responses. Further assessment of binding of Art v 125–36 to artificial HLA-DR molecules revealed that its affinity was high for HLA-DR1. Amino acid I27 was identified as anchor residue interacting with DR molecules in pocket P1. Additionally, Art v 125–36 bound with high affinity to HLA-DRB1*0301 and *0401, moderately to HLA-DRB1*1301 and HLA-DRB5*0101, and weakly to HLA-DRB1*1101 and *1501. T cell activation was also inducible by Art v 125–36-loaded, APC-expressing HLA molecules other than DR1, indicating degeneracy of peptide binding and promiscuity of TCR recognition. Specific binding of HLA-DRB1*0101 tetramers containing Art v 119–36 allowed the identification of Art v 125–36-specific T cells by flow cytometry. In summary, the immunodominance of Art v 125–36 relies on its affinity to DR1, but is not dictated by it. Future investigations at the molecular HLA/peptide/TCR and cellular level using mugwort pollen allergy as a disease model may allow new insights into tolerance and pathomechanisms operative in type I allergy, which may instigate new, T cell-directed strategies in specific immunotherapy.

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“…For example, HLA-DR*0401/peptide tetramers have been used to characterize Bos d 2 (bovine dander)-specific CD4+ T cells for the binding of altered peptides [80,81]. Applying HLA-DRB1*0401 tetramers loaded with the major epitope of rye grass Lol p 1, allergen-specific CD4+ T cells could be detected in the PB of DRB1*0401-positive rye grass allergic individuals after short-term expansion but not in nonallergic individuals [82].…”

Section: Current and Future Developments Based On Tcr/mhcp Interactiomentioning

confidence: 99%

Interaction of Allergens, Major Histocompatibility Complex Molecules, and T Cell Receptors: A ‘Ménage à Trois’ That Opens New Avenues for Therapeutic Intervention in Type I Allergy

Jahn‐Schmid

Pickl

Bohle

2011

Int Arch Allergy Immunol

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T cells are major players in the initiation and perpetuation of the allergic immune response. In this review, we summarize the current knowledge on allergen recognition by T lymphocytes and address the components of the trimeric recognition complex: T cell receptors, major histocompatibility complex molecules, and allergen-derived peptides. Furthermore, possible implications of this scientific background for future therapeutic developments are discussed.

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Potential of an altered peptide ligand of lipocalin allergen Bos d 2 for peptide immunotherapy

Cited by 30 publications

References 40 publications

Assessment of Bet v 1-Specific CD4+ T Cell Responses in Allergic and Nonallergic Individuals Using MHC Class II Peptide Tetramers

Assessment of Bet v 1-Specific CD4+ T Cell Responses in Allergic and Nonallergic Individuals Using MHC Class II Peptide Tetramers

Characterization of HLA Class II/Peptide-TCR Interactions of the Immunodominant T Cell Epitope in Art v 1, the Major Mugwort Pollen Allergen

Interaction of Allergens, Major Histocompatibility Complex Molecules, and T Cell Receptors: A ‘Ménage à Trois’ That Opens New Avenues for Therapeutic Intervention in Type I Allergy

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