Human CD8(+) T cells transduced with an additional receptor bispecific for both Mycobacterium tuberculosis and HIV-1 recognize both epitopes.
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 CD8(+) 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 CD8(+) 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 Ag85B199-207 peptide and HIV-1 Env120-128 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 CD8(+) T cells using a recombinant retroviral vector. The bispecificity of the TCR gene-modified CD8(+) 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 Ag85B199-207 or Env120-128 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 CD8(+) 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.
Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
Chao-Ying
CY
Zhou
Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
Qian
Q
Wen
Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
Xiao-Jie
XJ
Chen
Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
Rui-Ning
RN
Wang
Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
Wen-Ting
WT
He
Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
Shi-Meng
SM
Zhang
Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China.
Xia-Lin
XL
Du
Institute of Molecular Immunology, School of Biotechnology, Southern Medical University, Guangzhou, Guangdong, China. maryhmz@126.com.
Li
L
Ma
D000595:Amino Acid Sequence; D000941:Antigens / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D000945:Antigens, Differentiation, T-Lymphocyte / Q000378:metabolism; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D000939:Epitopes / Q000276:immunology*; D005822:Genetic Vectors / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D010455:Peptides / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D014161:Transduction, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099192:CD69 Antigens
D000941:Antigens; D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D000939:Epitopes; D007371:Interferon-gamma; D037181:Lectins, C-Type; D010455:Peptides; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha; D000099192:CD69 Antigens
CD8+ T cells; Mycobacterium tuberculosis; T cell receptor; adoptive immunotherapy; coinfection; cross-reactive; human immunodeficiency virus type 1