1 Div. of Infection and immunity, Joint Res. Center for Human Retrovirus infection, Kumamoto Univ.2 Dept. of Applied Chemistry, Faculty of Sci. and Eng., Kindai Univ.3 Dept. of Immunology, Faculty of Med., Academic Assembly, Toyama Univ.4 Grad. Sch. of Sci. and Eng., Kindai Univ.5 Dept. of Immunology, Kochi Univ. N-terminal modification of a SARS-CoV-2 Spike-derived epitope with a non-Cytotoxic T lymphocytes (CTLs) play a crucial role in controlling viral infections, and their functionality has a significant impact on disease outcomes. In SARS-CoV-2 infection, it is reported that T cell responses correlate with asymptomatic or mild disease. To enhance antiviral T cell responses, we developed novel T cell antigenic peptides incorporating non-canonical amino acids (ncAAs) as a novel modality. As a model, we used the highly immunogenic and conserved QI9 epitope (S1208–1216: QYIKWPWYI) from the SARS-CoV-2 spike protein, presented by HLA-A*24:02, prevalent in the Japanese population. The N-terminal modification of QI9 with ncAA induced stronger T cell responses in peripheral blood mononuclear cells (PBMCs) from vaccinated or convalescent donors in vitro. Moreover, immunization with the modified peptide elicited enhanced antigen-specific T cell responses and superior effector functions in HLA-A24 transgenic mice compared to the wild-type peptide in vivo. Collectively, these findings demonstrate that strategic incorporation of ncAAs into antigenic peptides can improve T cell immunogenicity and functionality, providing a promising approach for the development of next-generation T cell-based vaccines.canonical amino acid induces efficient T cell responses○Yoshiki Aritsu1 Amiri Kurose2 Hiroshi Hamana3 Takeshi Nakama1Kyoko Yamada1 Roran Ginoza1 Suzu Itami4 Huanyu Li1 Keiko Udaka5Hiroyuki Kishi3 Takamasa Ueno1 Norihito Kawashita4Mizuki Kitamatsu2 Chihiro Motozono145P 015
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