Elucidating molecular mechanisms of the regulation of immunodominance

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H03423
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 48040:Medical biochemistry-related
• Research Institution: The University of Tokyo
• Principal Investigator: Okazaki Il-mi 東京大学, 定量生命科学研究所, 准教授 (50452339)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 免疫ドミナンス / LAG-3 / 免疫偏向性

Outline of Final Research Achievements

We analyzed the possible involvement of an inhibitory co-receptor LAG-3 in the regulation of T cell immunodominance and revealed that LAG-3 selectively suppresses T cell responses towards dominant epitopes among many of immunogenic peptides, suggesting that LAG-3 mitigates immunodominance to ensure diversity of immune responses. We identified amino acid substitutions within the epitopes that affect binding to LAG-3. We also clarified LAG-3 sensitivity of T cells that express TCRs recognizing these epitopes with amino acid substitutions.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

免疫偏向性がどのように決定されるかについては多くの謎に包まれているが、ペプチド／MHCクラスIIとLAG-3の結合が免疫偏向性に与える影響を明らかにした。免疫応答の指向性が決定されるメカニズムが解明されれば、免疫応答を自在に操ることがより現実的となる。特に、がんや感染症に対するワクチン療法について、より効果的なワクチンのデザインが可能になると期待される。