TCR-mimic bispecific antibodies to target the HIV-1 reservoir

Significance Novel approaches to promote killing of HIV-1–infected cells are necessary for elimination of the latent reservoir, the main barrier to a cure. Here, we utilized a diverse phage-display library to construct T cell receptor (TCR)-mimic antibodies to HIV-1 peptide-major histocompatibility complexes (pMHC). We show that single-chain diabody forms of these antibodies recognize distinct epitopes in Gag and reverse transcriptase in a specific manner and induce T cell-mediated killing of HIV-1–infected CD4+ T cells. This study lays the groundwork for future exploration of pMHC-based immunotherapeutic approaches toward elimination of the latent reservoir once effective latency-reversing strategies are developed.