Open AccessHuman CD 8 + T cells transduced with an additional receptor bispecific for both Mycobacterium tuberculosis and HIV ‐1 recognize both epitopes
Author(s) -
Zhou ChaoYing,
Wen Qian,
Chen XiaoJie,
Wang RuiNing,
He WenTing,
Zhang ShiMeng,
Du XiaLin,
Ma Li
Publication year - 2016
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12878
Subject(s) - t cell receptor , epitope , antigen , virology , cytotoxic t cell , biology , mycobacterium tuberculosis , t cell , immunology , tuberculosis , adoptive cell transfer , microbiology and biotechnology , immune system , medicine , in vitro , biochemistry , pathology
Tuberculosis ( TB ) and human immunodeficiency virus type 1 ( HIV ‐1) infection are closely intertwined, with one‐quarter of TB / HIV coinfected deaths among people died of TB . Effector CD 8 + T cells play a crucial role in the control of Mycobacterium tuberculosis ( MTB ) and HIV ‐1 infection in coinfected patients. Adoptive transfer of a multitude of effector CD 8 + T cells is an appealing strategy to impose improved anti‐ MTB / HIV ‐1 activity onto coinfected individuals. Due to extensive existence of heterologous immunity, that is, T cells cross‐reactive with peptides encoded by related or even very dissimilar pathogens, it is reasonable to find a single T cell receptor ( TCR ) recognizing both MTB and HIV ‐1 antigenic peptides. In this study, a single TCR specific for both MTB Ag85B 199‐207 peptide and HIV ‐1 Env 120‐128 peptide was screened out from peripheral blood mononuclear cells of a HLA ‐A*0201 + healthy individual using complementarity determining region 3 spectratype analysis and transferred to primary CD 8 + T cells using a recombinant retroviral vector. The bispecificity of the TCR gene‐modified CD 8 + T cells was demonstrated by elevated secretion of interferon‐γ, tumour necrosis factor‐α, granzyme B and specific cytolytic activity after antigen presentation of either Ag85B 199‐207 or Env 120‐128 by autologous dendritic cells. To the best of our knowledge, this study is the first report proposing to produce responses against two dissimilar antigenic peptides of MTB and HIV ‐1 simultaneously by transfecting CD 8 + T cells with a single TCR . Taken together, T cells transduced with the additional bispecific TCR might be a useful strategy in immunotherapy for MTB / HIV ‐1 coinfected individuals.