@article{22101,
  keywords = {Amino Acid Sequence, Animals, B-Lymphocyte Subsets, Bacterial Proteins, Bacterial Vaccines, Cells, Cultured, Cytotoxicity Tests, Immunologic, Epitopes, T-Lymphocyte, HLA-A Antigens, HLA-A2 Antigen, Humans, leprosy, Mice, Mice, Transgenic, Molecular Sequence Data, Mycobacterium leprae, Peptide Fragments, T-Lymphocytes, Cytotoxic, T-Lymphocytes, Helper-Inducer, Vaccines, Subunit},
  author = {Geluk A and Eeden S and Dijkman K and Wilson L and Kim H and Franken K and Spencer JS and Pessolani MC V and Pereira GM and Ottenhoff T},
  title = {ML1419c peptide immunization induces Mycobacterium leprae-specific HLA-A*0201-restricted CTL in vivo with potential to kill live mycobacteria.},
  abstract = {<p>MHC class I-restricted CD8(+) T cells play an important role in protective immunity against mycobacteria. Previously, we showed that p113-121, derived from Mycobacterium leprae protein ML1419c, induced significant IFN-γ production by CD8(+) T cells in 90% of paucibacillary leprosy patients and in 80% of multibacillary patients' contacts, demonstrating induction of M. leprae-specific CD8(+) T cell immunity. In this work, we studied the in vivo role and functional profile of ML1419c p113-121-induced T cells in HLA-A*0201 transgenic mice. Immunization with 9mer or 30mer covering the p113-121 sequence combined with TLR9 agonist CpG induced HLA-A*0201-restricted, M. leprae-specific CD8(+) T cells as visualized by p113-121/HLA-A*0201 tetramers. Most CD8(+) T cells produced IFN-γ, but distinct IFN-γ(+)/TNF-α(+) populations were detected simultaneously with significant secretion of CXCL10/IFN-γ-induced protein 10, CXCL9/MIG, and VEGF. Strikingly, peptide immunization also induced high ML1419c-specific IgG levels, strongly suggesting that peptide-specific CD8(+) T cells provide help to B cells in vivo, as CD4(+) T cells were undetectable. An additional important characteristic of p113-121-specific CD8(+) T cells was their capacity for in vivo killing of p113-121-labeled, HLA-A*0201(+) splenocytes. The cytotoxic function of p113-121/HLA-A*0201-specific CD8(+) T cells extended into direct killing of splenocytes infected with live Mycobacterium smegmatis expressing ML1419c: both 9mer and 30mer induced CD8(+) T cells that reduced the number of ML1419c-expressing mycobacteria by 95%, whereas no reduction occurred using wild-type M. smegmatis. These data, combined with previous observations in Brazilian cohorts, show that ML1419c p113-121 induces potent CD8(+) T cells that provide protective immunity against M. leprae and B cell help for induction of specific IgG, suggesting its potential use in diagnostics and as a subunit (vaccine) for M. leprae infection.</p>},
  year = {2011},
  journal = {Journal of immunology (Baltimore, Md. : 1950)},
  volume = {187},
  pages = {1393-402},
  month = {2011 Aug 01},
  issn = {1550-6606},
  url = {https://www.jimmunol.org/content/jimmunol/187/3/1393.full.pdf},
  doi = {10.4049/jimmunol.1100980},
  language = {eng},
}