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

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 Gag(241-249) epitope, which is located in a region corresponding to the HIV Gag(240-249) 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-alpha and TCR-beta chains were obtained from a Gag(241-249) -specific CD8(+) T-cell clone. Coexpression of these TCR-alpha and TCR-beta cDNAs resulted in reconstitution of a functional TCR specifically detected by Gag(241-249) epitope-Mamu-A1*065:01 tetramer. Two of three previously-reported CD8(+) T-cell escape mutations reduced binding affinity of Gag(241-249) 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. (C) 2019 Elsevier Inc. All rights reserved.