MHC class I trafficking signal improves induction of cytotoxic T lymphocyte using artificial antigen presenting cells

作者：Kenta Sasaki, Kenji Murata, Tomoyuki Minowa, Naoki Shijubou, Hiroki Kobayashi, Munehide Nakatsugawa, Aiko Murai, Yuka Mizue, Terufumi Kubo, Takayuki Kanaseki, Tomohide Tsukahara, Hisashi Uhara, Akemi Ishida‐Yamamoto, Yoshihiko Hirohashi, Toshihiko Torigoe · 发表于：Biochemistry and Biophysics Reports · 年份：2025 · DOI：10.1016/j.bbrep.2025.101946 · 被引用次数：2 · 研究领域：Immune Cell Function and Interaction、T-cell and B-cell Immunology、Immunotherapy and Immune Responses

Inducing antigen peptide-specific cytotoxic T cells is challenging, partly due to the difficulty of maintaining the quality of antigen-presenting cells, such as dendritic cells. Consequently, artificial antigen-presenting cells (aAPCs) derived from the erythroleukemia cell line K562 have been employed for T cell stimulation. K562-based aAPCs can be utilized for both non-specific and antigen-specific T cell stimulation. Antigen peptide-pulsed aAPCs are commonly used to stimulate T cells with known specific antigenic peptides, which require identifying antigenic peptides from cognate antigen proteins. Therefore, antigen gene-overexpressing aAPCs might be useful for detecting unknown antigenic peptides. In this study, we evaluated the efficacy of cytotoxic T lymphocyte (CTL) induction using antigen gene-overexpressing aAPCs. To enhance antigen presentation efficiency, we assessed the signal peptide (SP) fused with MHC class I trafficking signal (MITD) sequences (SP-MITD). SP-MITD, fused with epitopes from the neoantigen AKF9 and the viral antigen CMVpp65, was transduced into aAPCs. We compared the CTL induction ability of peptide-pulsed aAPCs, only mini-gene-overexpressing aAPCs [SP-MITD (-)], and mini-gene fused with SP-MITD overexpressing aAPCs [SP-MITD (+)]. The SP-MITD (+) gene-overexpressing aAPCs exhibited the highest CTL induction efficiency compared to both peptide-pulsed and SP-MITD (-) gene-overexpressing aAPCs. These findings suggest that antigen gene-fused with SP-MI...