Role of conformational and linear epitopes in the achievement of tolerance in cow's milk allergy

Vila, Leticia; Beyer, Kirsten; Järvinen, Kirsi-Marjut; Chatchatee, Pantipa; Bardina, L.; Sampson, Hugh A.

doi:10.1046/j.1365-2222.2001.01218.x

Cited by 205 publications

(143 citation statements)

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“…Differences in recognition of specific epitopes have been described previously between patients with transient and persistent cow's milk allergy (14,19,35,36). It appeared that patients with persistent cow's milk allergy showed more frequent and more intense IgE reactivity and mediator release to r␣S1-casein and ␣S1-casein-derived peptides than did patients who had outgrown milk FIGURE 9.…”

Section: Discussionmentioning

confidence: 70%

Cloning, Expression, and Mapping of Allergenic Determinants of αS1-Casein, a Major Cow’s Milk Allergen

Schulmeister¹,

Hochwallner²,

Swoboda

et al. 2009

The Journal of Immunology

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Milk is one of the first components introduced into human diet. It also represents one of the first allergen sources, which induces IgE-mediated allergies in childhood ranging from gastrointestinal, skin, and respiratory manifestations to severe life-threatening manifestations, such as anaphylaxis. Here we isolated a cDNA coding for a major cow’s milk allergen, αS1-casein, from a bovine mammary gland cDNA library with allergic patients’ IgE Abs. Recombinant αS1-casein was expressed in Escherichia coli, purified, and characterized by circular dichroism as a folded protein. IgE epitopes of αS1-casein were determined with recombinant fragments and synthetic peptides spanning the αS1-casein sequence using microarrayed components and sera from 66 cow’s milk-sensitized patients. The allergenic activity of rαS1-casein and the αS1-casein-derived peptides was determined using rat basophil leukemia cells transfected with human FcεRI, which had been loaded with the patients’ serum IgE. Our results demonstrate that rαS1-casein as well as αS1-casein-derived peptides exhibit IgE reactivity, but mainly the intact rαS1-casein induced strong basophil degranulation. These results suggest that primarily intact αS1-casein or larger IgE-reactive portions thereof are responsible for IgE-mediated symptoms of food allergy. Recombinant αS1-casein as well as αS1-casein-derived peptides may be used in clinical studies to further explore pathomechanisms of food allergy as well as for the development of new diagnostic and therapeutic strategies for milk allergy.

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Section: Discussionmentioning

confidence: 70%

Cloning, Expression, and Mapping of Allergenic Determinants of αS1-Casein, a Major Cow’s Milk Allergen

Schulmeister¹,

Hochwallner²,

Swoboda

et al. 2009

The Journal of Immunology

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“…It has been described that some children who are allergic to HE are able to tolerate this food cooked but not raw (15). As suggested by Vila et aI., during food processing, heat and/or chemical processes can modify or disrupt many conformational epitopes, exposing linear epitopes (16). Moreover, Cooke & Sampson suggest that the development of IgE antibodies to these linear epitopes can be related to the persistence of HEA (17).…”

Section: Figures Indicate MM (Mean Oforthogonal Wheals Diameters)mentioning

confidence: 96%

Oral Desensitisation with Food is Food-Specific and Protein-Specific

Meglio¹,

Giampietro²,

Gabriele³

et al. 2011

Int J Immunopathol Pharmacol

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The avoidance of food(s) is the main therapeutic approach to food allergy. Nevertheless, orally-or sublingually-administered food allergens have gained attention and a number of food-allergic children can tolerate gradually increasing amounts of cow's milk and hen's egg. Our purpose is to show that oral desensitisation with food is an allergen-specific therapeutic approach and for this, we describe 4 illustrative children with IgE-mediated food allergy. The first was allergic to cow's milk and hen's egg, the second to cow's milk, hen's egg and fish. Both underwent oral desensitisation to both cow's milk and hen's egg. The third child was allergic to cow's milk, hen's egg and fish and underwent oral desensitisation with cow's milk. The last child was allergic to raw but not to cooked/boiled hen's egg and underwent the oral desensitisation with hen's egg. The first 2 children reached the clinical tolerance to cow's milk after the cow's milk oral desensitisation, but reached the hen's egg tolerance only after the hen's egg oral desensitisation. Moreover, the second child did not tolerate fish after being desensitised to both cow's milk and hen's egg. The third child tolerated cow's milk, but not hen's egg and fish, at the end of the cow's milk oral desensitisation. The fourth child could tolerate the previously not tolerated raw hen's egg after the oral desensitisation with raw hen's egg. In conclusion, we indicate that oral desensitisation with food is allergen specific. The induction of the clinical tolerance to one food is not followed by the tolerance to the other food(s) that the patient is allergic to. To obtain a double or multiple food tolerance, separate desensitisation protocols, one for each food, have to be carried out. Oral desensitisation with food discriminates between raw and cooked proteins.

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“…Recent studies have demonstrated that the persistency of CMA is associated with differences in IgE-binding epitopes to the different cow's milk proteins (CMPs). 3,4 Because T cells are responsible for the isotype switching of antigen-specific B cells to IgE, T-cell activation is the initial step in determination of the outcome of the immune response and plays a major role in the maintenance of the reaction. This might suggest that the observed differences in IgE-binding epitopes could be reflected in the CMPspecific T-cell pool.…”

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confidence: 99%

Cow's milk?specific T-cell reactivity of children with and without persistent cow's milk allergy: Key role for IL-10

Tiemessen

2004

Journal of Allergy and Clinical Immunology

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Background: The role of antigen-specific T cells in the mechanism of food allergy or maintenance of tolerance toward an innocuous antigen, such as cow's milk, is not yet fully understood. Objective: The cow's milk-specific T-cell response of donors with various allergic backgrounds was investigated. Methods: Cow's milk-specific T-cell clones (TCCs) were generated from the blood of children with persistent cow's milk allergy (CMA) and the blood of cow's milk-tolerant allergic and nonallergic control subjects. The TCCs were characterized by their antigen-specific proliferation, cytokine production, and activation status. Results: Cow's milk-specific TCCs of children with persistent CMA were T H 2 skewed, and the production of IL-4 and IL-13 was significantly correlated with the expression of the activation marker CD25. TCCs of the allergic control subjects were characterized by a high production of IL-10, which was positively correlated with the production of IL-4 and IFN-g and with the expression of CD25. TCCs derived from nonallergic control subjects had an attenuated response toward cow's milk in that they did not produce high levels of cytokines nor did they express high levels of surface markers. As in the allergic control subjects, in the nonallergic control subjects IL-10 production was positively correlated with the expression of CD25. Conclusion: The activation status of T cells derived from persistent donors with CMA was associated with the production of IL-4 and IL-13, whereas activated TCCs of cow's milktolerant control subjects were characterized by the production of IL-10 and, to a lesser extent, IFN-g. These findings suggest that activated CD4 + T cells (characterized by a high CD25 expression) might contribute to the tolerogenic immune response toward an antigen, such as cow's milk, through the production of

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Role of conformational and linear epitopes in the achievement of tolerance in cow's milk allergy

Cited by 205 publications

References 24 publications

Cloning, Expression, and Mapping of Allergenic Determinants of αS1-Casein, a Major Cow’s Milk Allergen

Cloning, Expression, and Mapping of Allergenic Determinants of αS1-Casein, a Major Cow’s Milk Allergen

Oral Desensitisation with Food is Food-Specific and Protein-Specific

Cow's milk?specific T-cell reactivity of children with and without persistent cow's milk allergy: Key role for IL-10

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