Determination of a T cell receptor of potent CD8+ T cells against simian immunodeficiency virus infection in Burmese rhesus macaques

Autor: Hiroshi Ishii, Takamasa Ueno, Tetsuro Matano, Kyoko Kurihara, Masaru Yokoyama, Akinori Kimura, Masafumi Takiguchi, Noriko Ikeda, Saori Matsuoka, Hironori Sato, Taeko K. Naruse
Rok vydání: 2020
Předmět:
Zdroj: Biochemical and Biophysical Research Communications. 521:894-899
ISSN: 0006-291X
DOI: 10.1016/j.bbrc.2019.10.196
Popis: Cumulative studies on human immunodeficiency virus (HIV)-infected individuals have shown association of major histocompatibility complex class I (MHC-I) polymorphisms with lower viral load and delayed AIDS progression, suggesting that HIV replication can be controlled by potent CD8+ T-cell responses. We have previously established an AIDS model of simian immunodeficiency virus (SIV) infection in Burmese rhesus macaques and found a potent CD8+ T cell targeting the Mamu-A1*065:01-restricted Gag241-249 epitope, which is located in a region corresponding to the HIV Gag240-249 TW10 epitope restricted by a protective MHC-I allele, HLA-B*57. In the present study, we determined a T cell receptor (TCR) of this Gag241-249 epitope-specific CD8+ T cell. cDNA clones encoding TCR-α and TCR-β chains were obtained from a Gag241-249-specific CD8+ T-cell clone. Coexpression of these TCR-α and TCR-β cDNAs resulted in reconstitution of a functional TCR specifically detected by Gag241-249 epitope-Mamu-A1*065:01 tetramer. Two of three previously-reported CD8+ T-cell escape mutations reduced binding affinity of Gag241-249 peptide to Mamu-A1*065:01 but the remaining one not. This is consistent with the data obtained by molecular modeling of the epitope-MHC-I complex and TCR. These results would contribute to understanding how viral CD8+ T-cell escape mutations are selected under structural constraint of viral proteins.
Databáze: OpenAIRE
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