MHC-restricted Ag85B-specific CD8+ T cells are enhanced by recombinant BCG prime and DNA boost immunization in mice.
Shihoko Komine-AizawaJiansheng JiangSatoru MizunoSatoshi HayakawaKazuhiro MatsuoLisa F BoydDavid H MarguliesMitsuo HondaPublished in: European journal of immunology (2019)
Despite efforts to develop effective treatments and vaccines, Mycobacterium tuberculosis (Mtb), particularly pulmonary Mtb, continues to provide major health challenges worldwide. To improve immunization against the persistent health challenge of Mtb infection, we have studied the CD8+ T cell response to Bacillus Calmette-Guérin (BCG) and recombinant BCG (rBCG) in mice. Here, we generated CD8+ T cells with an rBCG-based vaccine encoding the Ag85B protein of M. kansasii, termed rBCG-Mkan85B, followed by boosting with plasmid DNA expressing the Ag85B gene (DNA-Mkan85B). We identified two MHC-I (H2-Kd )-restricted epitopes that induce cross-reactive responses to Mtb and other related mycobacteria in both BALB/c (H2d ) and CB6F1 (H2b/d ) mice. The H2-Kd -restricted peptide epitopes elicited polyfunctional CD8+ T cell responses that were also highly cross-reactive with those of other proteins of the Ag85 complex. Tetramer staining indicated that the two H2-Kd -restricted epitopes elicit distinct CD8+ T cell populations, a result explained by the X-ray structure of the two peptide/H2-Kd complexes. These results suggest that rBCG-Mkan85B vector-based immunization and DNA-Mkan85B boost may enhance CD8+ T cell response to Mtb, and might help to overcome the limited effectiveness of the current BCG in eliciting tuberculosis immunity.
Keyphrases
- mycobacterium tuberculosis
- pulmonary tuberculosis
- cell free
- circulating tumor
- single molecule
- quantum dots
- high fat diet induced
- healthcare
- public health
- mental health
- escherichia coli
- randomized controlled trial
- systematic review
- high resolution
- emergency department
- pulmonary hypertension
- magnetic resonance imaging
- circulating tumor cells
- visible light
- risk assessment
- type diabetes
- genome wide
- human health
- insulin resistance
- metabolic syndrome
- climate change
- protein protein
- electronic health record
- skeletal muscle
- health promotion