The search for HLA inhibitor using short ragweed allergy mouse model.

• Project/Area Number: 25713058
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Ophthalmology
• Research Institution: Yokohama City University
• Principal Investigator: KAWAGOE Tatsukata 横浜市立大学, 医学部, 助教 (20564800)
• Research Collaborator: HIRAYAMA Noriaki 東海大学, 医学部, 教授 (70238393)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥8,450,000 (Direct Cost: ¥6,500,000、Indirect Cost: ¥1,950,000); Fiscal Year 2014: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2013: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
• Keywords: アレルギー

Outline of Final Research Achievements

The aim of this study is to search the low molecular compounds that bind to HLA and inhibit T cell mediated allergic reaction.
Using in silico screening methods, we determined high affinity chemical compounds to HLA-DQ6 and DQ8 from 6 million chemical libraries. We identified 49 compounds in each HLA. By some technical problems in the experiments, the progress is behind the schedule. We are still creating transgenic mice expressing HLA-DQ6 (HLA-DQA1*0103, HLA-DQB1*0601) and DQ8 (HLA-DQA1*0301, HLA-DQB1*0302) genes in H2 class II knockout mice. We will immunize these mice with short ragweed (Ambrosia artemisiifolia) extracts or known epitopes, and demonstrate the identified chemical compounds inhibit T cell reaction. The humanized mouse model of allergy could be the screening model of HLA inhibitor. We will continuously develop a novel treatment of allergy.