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

• Published in: Japanese Journal of Infectious Diseases Vol. 71; no. 2; pp. 122 - 128
• Main Authors: Ono, Toshiaki, Fujita, Yuriko, Matano, Tetsuro, Takahashi, Satoshi, Morio, Tomohiro, Kawana-Tachikawa, Ai
• Format: Journal Article
• Language: English
• Published: Japan National Institute of Infectious Diseases, Japanese Journal of Infectious Diseases Editorial Committee 2018; Japan Science and Technology Agency
• Subjects: Adoptive immunotherapy; Adoptive transfer; BZLF1 protein; CD4 antigen; CD8 antigen; Cryopreservation; Cytomegalovirus; ELISpot; Epitope mapping; Epstein-Barr virus; HLA restriction; IE1 protein; Immunocompromised hosts; Immunotherapy; Interleukin 7; Leukocytes (mononuclear); Lymphocytes; Lymphocytes T; Peptide mapping; Peptides; Peripheral blood mononuclear cells; Pp65 protein; Predictions; Proteins; T cell adoptive transfer; T cell receptors; virus-specific T cells; Viruses; virus-specific T cells; HLA restriction; T cell adoptive transfer; ELISpot; epitope mapping
• ISSN: 1344-6304; 1884-2836; 1884-2836
• DOI: 10.7883/yoken.JJID.2017.500

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.