[Sep. 14] 94th IRCMS Seminar

September 1 2023

We would like to inform you that the 94th IRCMS seminar has been scheduled as below.
* This IRCMS seminar is open to everyone.

Date      : September 14, 2023 (Thursday)

Time      : 16:00-17:00

ZOOM　: Meeting ID: 884 5562 8103
            　Passcode: IRCMSc2c

Speaker : Dr. Takumi Maruhashi
                 University of Tokyo

Title        :  Immune regulation by LAG-3, a unique inhibitory co-receptor

Abstract :

Lymphocyte-activation gene 3 (LAG-3), an inhibitory co-receptor, plays a key role in the regulation of autoimmunity, tumor immunity and infectious immunity. LAG-3 attracts increasing interest as a therapeutic target beyond PD-1 and CTLA-4, whereas many of the basic properties of LAG-3, such as ligand specificity and inhibitory mechanisms, remain unelucidated. Although LAG-3 has been reported to bind to MHC class II, we found that LAG-3 did not recognize MHC class II universally but instead selectively recognizes conformationally stable complexes of peptides and MHC class II (pMHCII). Thereby, LAG-3 selectively suppressed the activation of CD4⁺ T cells responsive to stable but not unstable pMHCII to suppress autoimmunity and anti-cancer immunity, and the inhibitory effect was mediated through its cytoplasmic region. In this seminar, I will introduce these recent studies demonstrating a unique property of LAG-3 as an immunoinhibitory co-receptor.

1. Maruhashi T, Sugiura D, Okazaki IM, Shimizu K, Maeda TK, Ikubo J, Yoshikawa H, Maenaka K, Ishimaru N, Kosako H, Takemoto T, Okazaki T. "Binding of LAG-3 to stable peptide-MHC class II limits T cell function and suppresses autoimmunity and anti-cancer immunity" Immunity. 2022 Apr 5:S1074-7613(22)00136-4.
2. Maruhashi T, Sugiura D, Okazaki IM, Okazaki T. "LAG-3: From molecular functions to clinical applications" Journal of Immunotherapy of Cancer. 2020 Sep;8(2):e001014.
3. Maruhashi T, Okazaki IM, Sugiura D, Takahashi S, Maeda TK, Shimizu K, Okazaki T. "LAG-3 inhibits the activation of CD4+ T cells that recognize stable pMHCII through its conformation-dependent recognition of pMHCII" Nat Immunol. 2018 Dec;19(12):1415-1426.

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