MHC‐restricted Ag85B‐specific CD8+ T cells are enhanced by recombinant BCG prime and DNA boost immunization in mice. Issue 9 (19th June 2019)

• Record Type: Journal Article
• Authors: Komine‐Aizawa, Shihoko; Jiang, Jiansheng; Mizuno, Satoru; Hayakawa, Satoshi; Matsuo, Kazuhiro; Boyd, Lisa F.; Margulies, David H.; Honda, Mitsuo
• Is Part Of: European journal of immunology. Volume 49:Issue 9(2019)
• Page Start: 1399
• Page End: 1414
• Publication Date: 2019-06-19
• Subjects: CD4+ T Cells -- CD8+ T Cells -- MHC‐I presentation -- Mycobacterium tuberculosis, recombinant BCG; Immunology -- Periodicals; 616.079
• DOI: 10.1002/eji.201847988
• Languages: English
• ISSNs: 0014-2980

Abstract

Abstract: 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‐K d )‐restricted epitopes that induce cross‐reactive responses to Mtb and other related mycobacteria in both BALB/c (H2 d ) and CB6F1 (H2 b/d ) mice. The H2‐K d ‐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‐K d ‐restricted epitopes elicit distinct CD8 + T cell populations, a result explained by the X‐ray structure of the two peptide/H2‐K d 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. Abstract : Ag85B specific polyfunctional CD8 + T cells are inducible by recombinant BCG encoding the Ag85B protein of Mycobacterium kansasii (rBCG‐Mkan85B), followed by boosting with plasmid DNA expressing the Ag85B gene (DNA‐Mkan85B). We identified two MHC‐I (H2‐K d )‐restricted epitopes that induce cross‐reactive responses to M. tuberculosis and other mycobacteria.