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Aralysis of antigen presentation mechanisms and development of therapy for food allergy

食物过敏抗原呈递机制分析及治疗进展

基本信息

批准号：
04660079
负责人：
AMETANI Akio
金额：
$ 1.47万
依托单位：
The University of Tokyo
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1992
资助国家：
日本
起止时间：
1992 至 1994
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04660079/
关键词：
Antigen presentation Antigen processing mouse Antigen-presenting cells T cell Antigenic determinant Food allergy イタン-フェロン γ 抗原プロセシング T細胞抗原決定基 B-ラクトグロブリン MHCクラスII分子鶏卵白リゾチームプロテイナーゼ

项目摘要

Antigen presentation to T cells specific for the antigenic proteins from food of milk and egg white was studied by using a mouse model. A T cell determinant (regions 87-96 in hen egg white lysozyme (HEL) restricted to E^k) was categorized to be a cryptic determinant from the criteria that immunization of B10. A mice with the whole protein of HEL did not induce a T cell response, but that with a short peptide of p85-96 did strongly. Each type of antigen-presenting cells (APC) presented some determinants preferentially : in vitro some type of APC presented 87-96/E^k which other APC could not present. These suggest that APC able to prime response of naive T cell response in vivo cannot present 87-96/E^k, even if other APC only able to stimulate memory and/or activated T cells can. Interferron-gamma affected these antigen presentation patterns positively or negatively. This affection was also various among APC types and determinant specificity. In orally tolerant C3H/He mice fed with bovine alpha_<s1>-casein, T cells specific for the dominant determinants were tolerized, while those for the cryptic or subdominant ones were not. These indicate that antigen presentation patterns were various among APC types, and affected by some inflamatory cytokines. These allow us to present a model for excessive T cell response found in autoimmunity and food allergy : T cells specific for cryptic determinants in self antigen or food antigen are not tolerized, even if self tolerance or oral tolerance to food antigen is established. Those T cells can be activated in case that antigen presentation pattern changed due to aberrant secretion of some cytokines or that unexpected types of APC which have a potential of unusual antigen presentation encounter these antigen protein. This study will be helpful for development of antigen-specific therapy of the diseases related to excessive immune responses.

用小鼠模型研究了牛奶和蛋清白色食物中抗原蛋白对T细胞的抗原提呈。根据B10免疫的标准，将T细胞决定簇（鸡蛋白色溶菌酶（HEL）中限制于E^k的区域87-96）归类为隐蔽决定簇。用HEL全蛋白的小鼠不能诱导T细胞应答，而用p85-96短肽的小鼠则能诱导强烈的T细胞应答。每种类型的抗原呈递细胞（APC）优先呈递某些决定簇：在体外，某些类型的APC呈递87-96/E^k，而其他APC不能呈递。这些表明，能够在体内引发初始T细胞应答的APC不能呈递87-96/Ek，即使仅能够刺激记忆和/或活化的T细胞的其他APC可以。干扰素-γ影响这些抗原呈递模式积极或消极。这种影响在APC类型和决定簇特异性之间也是不同的。在口服耐受牛α-酪蛋白的C3 H/He小鼠中<s1>，对显性决定簇特异的T细胞被耐受，而对隐性或亚显性决定簇特异的T细胞则不被耐受。这些结果表明，不同类型APC的抗原提呈模式不同，并受一些炎症细胞因子的影响。这些使我们能够提出在自身免疫和食物过敏中发现的过度T细胞应答的模型：即使建立了对食物抗原的自身耐受性或口服耐受性，对自身抗原或食物抗原中的隐蔽决定簇特异性的T细胞也不耐受。在由于某些细胞因子的异常分泌而改变抗原呈递模式的情况下，或者在具有异常抗原呈递潜力的意外类型的APC遇到这些抗原蛋白的情况下，这些T细胞可以被激活。本研究将有助于开发与过度免疫反应相关疾病的抗原特异性治疗。