Open AccessTCR-mimic bispecific antibodies to target the HIV-1 reservoir
Author(s) -
Srona Sengupta,
Nathan L Board,
Fengting Wu,
Milica Moskovljevic,
Jacqueline Douglass,
Josephine Zhang,
Bruce B. Reinhold,
Jonathan S. DukeCohan,
Jeanna Yu,
Madison Reed,
Yasmine Tabdili,
Aitana Azurmendi,
Emily J. Fray,
Hao Zhang,
Emily HanChung Hsiue,
Katharine M. Jenike,
Ya-Chi Ho,
Sandra B. Gabelli,
Kenneth W. Kinzler,
Bert Vogelstein,
Shibin Zhou,
Janet D. Siliciano,
Scheherazade SadeghNasseri,
Ellis L. Reinherz,
Robert F. Siliciano
Publication year - 2022
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2123406119
Subject(s) - t cell receptor , epitope , biology , virology , antibody , t cell , antigen , major histocompatibility complex , immune system , microbiology and biotechnology , immunology
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.