Aralysis of antigen presentation mechanisms and development of therapy for food allergy
| Project/Area Number |
04660079
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
応用生物化学・栄養化学
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| Research Institution | The University of Tokyo |
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Principal Investigator |
AMETANI Akio The University of Tokyo, Faculty of Agriculture, Associate Professor, 農学部, 助教授 (50201900)
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| Project Period (FY) |
1992 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1993: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | 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 |
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| Research Abstract |
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.
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Report
(4 results)
Research Products
(23 results)
