Characterization of In Vitro Expanded Virus-Specific T cells for Adoptive Immunotherapy against Virus Infection

Jpn J Infect Dis. 2018 Mar 22;71(2):122-128. doi: 10.7883/yoken.JJID.2017.500. Epub 2018 Feb 28.


Adoptive transfer of virus-specific T cells has emerged as a promising therapeutic approach for treatment of virus infections in immunocompromised hosts. Characterization of virus-specific T cells provides essential information about the curative mechanism of the treatment. In this study, we developed a T cell epitope mapping system for 718 overlapping peptides spanning 6 proteins of 3 viruses (pp65 and IE1 from cytomegalovirus; LMP1, EBNA1, and BZLF1 from Epstein-Barr virus; Penton from adenovirus). Peripheral blood mononuclear cells (PBMCs) from 33 healthy Japanese donors were stimulated with these peptides and virus-specific CD4+ and CD8+ T cells were expanded in vitro in the presence of interleukin (IL) 4 and IL7. A median of 13 (minimum-maximum, 2-46) peptides was recognized in the cohort. Both fresh and cryopreserved PBMCs were used for in vitro expansion. The expansion and breadth of T cell responses were not significantly different between the 2 PBMC sets. We assessed viral regions frequently recognized by T cells in a Japanese cohort that could become pivotal T cell targets for immunotherapy in Japan. We tested epitope prediction for CD8+ T cell responses against a common target region using a freely available online tool. Some epitopes were considered to be predictive.

Keywords: ELISpot; HLA restriction; T cell adoptive transfer; epitope mapping; virus-specific T cells.

MeSH terms

  • Antigens, Viral / immunology
  • CD4-Positive T-Lymphocytes / chemistry
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / chemistry
  • CD8-Positive T-Lymphocytes / immunology*
  • Epitopes, T-Lymphocyte
  • Gene Frequency
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Virus Diseases / immunology
  • Virus Diseases / therapy*
  • Virus Diseases / virology
  • Viruses / genetics
  • Viruses / immunology


  • Antigens, Viral
  • Epitopes, T-Lymphocyte