| Research Abstract |
Increase in the number of patients with allergies or autoimmune diseases have aroused the demand for developing safe and efficient means of treatment for these diseases. We aimed to develop such treatment by means of food proteins and peptides, and their amino-acid substituted analogs. 1.T-and B-cell responses to food allergens or a homologue of a self-antigen were analyzed in mice and in patients allergic to cow's milk. 2.Antigenic structure of beta-lactoglobulin, a major milk allergen, was analyzed in detail. Single amino-acid substituted analogs of beta-lactoglobulin or its partial peptide were examined for their inhibitory effect on allergen-specific immune responses, and shown to be effective. Moreover, we showed that single substituted analogs of a peptide from alpha_<s1>-casein, another major milk allergen, could modulate the CD8^+T-cell responses to the allergen. 3.The condition required for and the mechanism of induction of oral tolerance was investigated. We clarified the roles of CD4^+T cells, CD8^+T cells, and B cells, and the relationship between the dose of orally administered antigen and the induction of oral tolerance. Furthermore, the immune responses to orally administered antigens, including those of the gut-associated lymphoid tissue, were analyzed using T-cell receptor transgenic mice. 4.A novel means of inhibition of allergic or autoimmune responses was investigated. We showed that administration of protein or peptide antigens related to food allergens or self-antigens can efficiently inhibit antigen-specific immune responses in vivo. The use of anti-T-cell response was also shown to be effective in inhibiting autoimmune responses. We believe that the findings obtained in this study provide us with information useful not only for developing a novel way of treatment and prevention from allergies and autoimmune diseases but also for elucidating the mechanisms of oral tolerance, antigen recognition by immune system and onset of these diseases.
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