Inhibition of allergic and autoimmune responses by means of food proteins and peptides.

过敏或自身免疫性疾病患者数量的增加引起了对开发安全有效的治疗这些疾病的方法的需求。我们的目标是通过食品蛋白质和多肽及其氨基酸取代类似物来开发这种处理方法。1.在小鼠和对牛奶过敏的患者中，分析了T细胞和B细胞对食物过敏原或自身抗原的同系物的反应。2.详细分析了牛奶主要变应原β-乳球蛋白的抗原性结构。单一氨基酸取代的β-乳球蛋白类似物或其部分肽被检测其对过敏原特异性免疫反应的抑制作用，并被证明是有效的。此外，我们还发现，来自另一种主要牛奶变应原-酪蛋白的单一取代类似物可以调节CD8^T细胞对该变应原的反应。3.探讨了诱导口服耐受性的条件和机制。我们阐明了CD_4~+T细胞、CD_8~+T细胞和B细胞的作用，以及口服抗原剂量与诱导口服耐受的关系。此外，使用T细胞受体转基因小鼠分析了口服抗原，包括肠道相关淋巴组织的抗原的免疫应答。4.研究了抑制变态反应或自身免疫反应的新方法。我们发现，在体内注射与食物过敏原或自身抗原相关的蛋白质或多肽抗原可以有效地抑制抗原特异性免疫反应。抗T细胞反应的使用也被证明在抑制自身免疫反应方面是有效的。我们相信，这项研究的结果不仅为开发治疗和预防过敏和自身免疫性疾病的新途径提供了有用的信息，也为阐明口服耐受、免疫系统识别抗原和这些疾病的发病机制提供了有用的信息。

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.