Characterization of T cell epitopes in αs1‐casein in cow's milk allergic, atopic and non‐atopic children

Ruiter, Bert; Tregoat, Virginie; M’Rabet, Laura; Garssen, Johan; Bruijnzeel-Koomen, Carla A.F.M.; Knol, Edward F.; Hoffen, Els van

doi:10.1111/j.1365-2222.2006.02436.x

Cited by 59 publications

(47 citation statements)

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“…Cow's milk allergy is the most common food allergy in young children, affecting 1-2% of all infants [18]. Casein represents a major allergen in cow's milk [3] and consists of four proteins: α S1 -casein, α S2 -casein, β-casein and κ-casein, representing 32%, 10%, 28%, and 10%, respectively, of the total milk protein [17]. Of these four proteins, α S1 -casein thought to be the most potent for inducing a specific IgE response [1].…”

Section: Introductionmentioning

confidence: 99%

Expression of a Biologically Active GFP-αS1-Casein Fusion Protein in Lactococcus lactis

et al. 2012

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Section: Introductionmentioning

confidence: 99%

Expression of a Biologically Active GFP-αS1-Casein Fusion Protein in Lactococcus lactis

et al. 2012

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“…The major allergens of cow's milk (CM) are betalactoglobulin (b-LG) and alpha-S1-casein, as indicated by large population studies (3). These proteins are also highly resistant to proteolysis by gastrointestinal enzymes, resulting in large peptides at the site of mucosal immune system with implications for immune reactivity and cow's milk allergy (CMA) emergence (4).…”

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confidence: 99%

Peripheral Blood Immune Response Elicited by Beta-Lactoglobulin in Childhood Cow's Milk Allergy

et al. 2011

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Several studies analyzing the immune responses in patients with cow's milk allergy (CMA) have used T-cell lines or T-cell clones that require prolonged in vitro cell culturing and may result in a switched cell phenotype and function. We investigated immune responses to beta-lactoglobulin (b-LG) in peripheral blood mononuclear cells after a short in vitro antigen stimulation in children with acute CMA (both IgE-mediated and non-IgE-mediated forms) and in those who outgrew an IgE-mediated CMA. Healthy controls were also investigated. Peripheral blood mononuclear cells were assayed for IL-13, IFN-␥, IL-4, and IL-10. Although b-LG induced a cytokine production and/or cell proliferation almost in all children, included healthy controls, differences were observed among the four groups. Children with IgE-mediated CMA had a marked Th2-response, with high IL-13 production and proliferation, but low IFN-␥; by contrast, children with non-IgE-mediated CMA produced no, or very low, IL-13 and cell proliferation. Children, who outgrew CMA, showed a shift to a Th1-response, with reduced IL-13 and increased IFN-␥. IL-10-responses were high in all groups, with the highest level in healthy children; by contrast, IL-4 was undetectable in all children. This study highlights the use of shortly stimulated peripheral blood cells to investigate the food-induced immune responses. (Pediatr Res 70: 549-554, 2011)

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“…T cells epitopes have been mapped in a number of food allergens including the cow's milk allergen αs1-casein [53], peanut allergen Ara h 2 [54], peach allergen Pru p 3 [41], egg allergen ovalbumin (OVA) [42] and egg-white allergen ovomucoid (Ovm) [55]. However, investigations on the feasibility of these epitopes being utilized in PIT and the possible clinical outcome were restricted to egg allergy to date.…”

Section: Applications Of T Cell Epitopes In Therapymentioning

confidence: 99%

From Molecule Studies of Allergens to Development of Immunotherapy of Allergies

Wai¹,

Leung²,

Chu³

et al. 2012

J Aller Ther

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IntroductionAllergy is a type I hypersensitivity disease prominently influences the quality of life. Allergens can strike one through the administration of drugs, insect sting, and ingestion of food or simply inhalation, making patients hard to strictly avoid these molecules. Allergen specific immunotherapy for grass pollen allergy has been put into clinical trials since 1950s and demonstrated satisfactory therapeutic effects [1]. It therefore paves the way for extensive researches on designing different allergen specific immunotherapy and unveiling the underlying mechanisms of these therapies.Defining the immunological mechanisms leading to allergy is crucial in designing allergen-specific immunotherapy. Sensitization of allergic individuals to allergens is initialized upon presentation of the allergen-derived peptides by the antigen presenting cells (APCs) through the major histocompatibility class II molecule (MHC class II) to naïve T cells, which are then activated and differentiated into type 2 T helper cells (Th2) (Figure 1). Cytokines such as IL-4 and IL-13 from Th2 cause a class switch in B cells to produce IgE antibodies specific to the particular allergen. When the individual is exposed to the same allergen again, IgE are massively produced, cross-link with the allergen and high affinity receptor (FcεRI) on mast cells and induce degranulation. Mediators such as histamine and leukotriene are released, resulting in inflammation and other associated anaphylactic responses [2].Molecular characteristics of allergens, in particular the identification of T cell and B cell epitopes, constitute important information for the design of therapeutic regimens. T cell epitopes refer to the short peptide fragments activating Th2 via MHC class II molecules while B cell epitopes, or IgE-binding epitopes, refer to the regions recognized by IgE on the allergen. With the identification of B cell epitopes at the molecular level, hypo-allergens possessing reduced allergenicity can be constructed through the introduction of point mutations on these IgE-binding regions [3,4]. The lack of IgE reactivity reduces the risk of these hypo-allergens to form cross-links with IgE and thus prevents the development of allergic side effects during treatment [5]. Meanwhile, since the T cell epitopes are conserved, these hypo-allergens are immunogenic and thus offer therapeutic effects. Alternatively, the employment of T cell epitopes in immunotherapy is believed to be a potential strategy since small peptide fragments are incapable to form cross-link with IgE but yet immunogenic to modulate immune responses [6]. AbstractAllergies are hypersensitive reactions that affect over 25% of the world population. Extensive studies have been directed to define patho-immunological mechanisms of allergy and the molecular characteristics of allergens. The emerging B cell and T cell epitope database has greatly facilitated the development of epitope-based immunotherapy that aims at modulating patients' immune responses towards a specific allergen. Modifi...

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Characterization of T cell epitopes in αs1‐casein in cow's milk allergic, atopic and non‐atopic children

Cited by 59 publications

References 21 publications

Expression of a Biologically Active GFP-αS1-Casein Fusion Protein in Lactococcus lactis

Expression of a Biologically Active GFP-αS1-Casein Fusion Protein in Lactococcus lactis

Peripheral Blood Immune Response Elicited by Beta-Lactoglobulin in Childhood Cow's Milk Allergy

From Molecule Studies of Allergens to Development of Immunotherapy of Allergies

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