Evaluation of the ability of N-terminal fragment of lethal factor of Bacillus anthracis for delivery of Mycobacterium T cell antigen ESAT-6 into cytosol of antigen presenting cells to elicit effective cytotoxic T lymphocyte response.
We report the ability of N-terminal fragment of lethal factor of Bacillus anthracis to deliver genetically fused ESAT-6 (early secretory antigen target), a potent T cell antigen of Mycobacterium tuberculosis, into cytosol to elicit Cytotoxic T lymphocyte (CTL) response. In vitro Th1 cytokines data and CTL assay proved that efficient delivery of LFn.ESAT-6 occurs in cytosol, in the presence of protective antigen (PA), and leads to generation of effective CTL response. Since CTL response is essential for protection against intracellular pathogens and, it is well known that only single T cell epitope or single antigenic protein is not sufficient to elicit protective CTL response due to variation or polymorphism in MHC-I alleles among the individuals, we suggest that as a fusion protein LFn can be used to deliver multiepitopes of T cells or multiproteins which can generate effective CTLs against intracellular pathogens like M. tuberculosis. It can be used to enhance the protective efficacy of BCG vaccine.
Chandra
Subhash
S
Center for Biotechnology, Jawaharlal Nehru University, New Delhi 110067, India.
Kaur
Manpreet
M
Midha
Shuchi
S
Bhatnagar
Rakesh
R
Banerjee-Bhatnagar
Nirupama
N
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology*; D000942:Antigens, Bacterial / Q000008:administration & dosage* / Q000276:immunology*; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D001426:Bacterial Proteins / Q000008:administration & dosage* / Q000276:immunology*; D001427:Bacterial Toxins / Q000008:administration & dosage / Q000276:immunology*; D002478:Cells, Cultured; D003600:Cytosol / Q000276:immunology / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D001427:Bacterial Toxins; C093276:ESAT-6 protein, Mycobacterium tuberculosis; D011993:Recombinant Fusion Proteins; C030325:anthrax toxin