Generation mechanism of Neo-self by metal / chemical

2020 Fiscal Year Final Research Report

• Project Area: Creation, function and structure of neo-self
• Project/Area Number: 16H06497
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Tohoku University
• Principal Investigator: Kouetsu Ogasawara 東北大学, 加齢医学研究所, 教授 (30323603)
• Project Period (FY): 2016-06-30 – 2021-03-31
• Keywords: MHC

Outline of Final Research Achievements

In this study, we investigated the molecular mechanism by which the antigen peptide-MHC complex modified by haptens as “neo-self”. To explore the mechanisms, we analyzed T cell receptors that react with haptens such as metal. We identified the metal allergy-specific T cell receptors in a mouse model of metal allergy using palladium (Pd). Furthermore, by in vitro cell culture system, we found that the antigen peptide-MHC complex was changed by Pd solution and the expression of MHC was transiently reduced. In other words, we found that the behavior of the antigen peptide-MHC complex induces changes in the repertoire of T cell receptors. Therefore, our findings suggest that the behavior of antigen peptide-MHC complex may be induce the neo-self.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究では、金属がハプテンとして機能するだけでなく、抗原ペプチド-MHC 複合体が パラジウム溶液によって変化し、MHC の発現が一過性に低下することを見出した。 つまり、抗原ペプチド-MHC複合体の挙動がT細胞受容体のレパートリーの変化を誘導した。我々の発見は、MHCの挙動を変化させることで、MHCが新たな自己抗原を認識する機構であるネオ・セルフという現象を示す結果を得た。すなわち、ネオ・セルフという概念の実証を示したという学術的意義を持つ。