PT - JOURNAL ARTICLE AU - Chihiro Motozono AU - Mako Toyoda AU - Jiri Zahradnik AU - Terumasa Ikeda AU - Akatsuki Saito AU - Toong Seng Tan AU - Isaac Ngare AU - Hesham Nasser AU - Izumi Kimura AU - Keiya Uriu AU - Yusuke Kosugi AU - Shiho Torii AU - Akiko Yonekawa AU - Nobuyuki Shimono AU - Yoji Nagasaki AU - Rumi Minami AU - Takashi Toya AU - Noritaka Sekiya AU - Takasuke Fukuhara AU - Yoshiharu Matsuura AU - Gideon Schreiber AU - The Genotype to Phenotype Japan (G2P-Japan) consortium AU - So Nakagawa AU - Takamasa Ueno AU - Kei Sato TI - An emerging SARS-CoV-2 mutant evading cellular immunity and increasing viral infectivity AID - 10.1101/2021.04.02.438288 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.04.02.438288 4099 - http://biorxiv.org/content/early/2021/04/05/2021.04.02.438288.short 4100 - http://biorxiv.org/content/early/2021/04/05/2021.04.02.438288.full AB - During the current SARS-CoV-2 pandemic that is devastating the modern societies worldwide, many variants that naturally acquire multiple mutations have emerged. Emerging mutations can affect viral properties such as infectivity and immune resistance. Although the sensitivity of naturally occurring SARS-CoV-2 variants to humoral immunity has recently been investigated, that to human leukocyte antigen (HLA)-restricted cellular immunity remains unaddressed. Here we demonstrate that two recently emerging mutants in the receptor binding domain of the SARS-CoV-2 spike protein, L452R (in B.1.427/429) and Y453F (in B.1.298), can escape from the HLA-24-restricted cellular immunity. These mutations reinforce the affinity to viral receptor ACE2, and notably, the L452R mutation increases protein stability, viral infectivity, and potentially promotes viral replication. Our data suggest that the HLA-restricted cellular immunity potentially affects the evolution of viral phenotypes, and the escape from cellular immunity can be a further threat of the SARS-CoV-2 pandemic.Competing Interest StatementThe authors have declared no competing interest.