Epitopes described in "Potential contribution of a novel Tax epitope-specific CD4+ T cells to graft-versus-Tax effect in adult T cell leukemia patients after allogeneic hematopoietic stem cell transplantation."

Article Authors:Yotaro Tamai; Atsuhiko Hasegawa; Ayako Takamori; Amane Sasada; Ryuji Tanosaki; Ilseung Choi; Atae Utsunomiya; Yasuhiro Maeda; Yoshihisa Yamano; Tetsuya Eto; Ki-Ryang Koh; Hirohisa Nakamae; Youko Suehiro; Koji Kato; Shigeki Takemoto; Jun Okamura; Naokuni Uike; Mari Kannagi
Article Title:Potential contribution of a novel Tax epitope-specific CD4+ T cells to graft-versus-Tax effect in adult T cell leukemia patients after allogeneic hematopoietic stem cell transplantation.
Reference Detail
Reference ID:1025685
Abstract:Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for adult T cell leukemia/lymphoma (ATL) caused by human T cell leukemia virus type 1 (HTLV-1). We previously reported that Tax-specific CD8(+) cytotoxic T lymphocyte (CTL) contributed to graft-versus-ATL effects in ATL patients after allo-HSCT. However, the role of HTLV-1-specific CD4(+) T cells in the effects remains unclear. In this study, we showed that Tax-specific CD4(+) as well as CD8(+) T cell responses were induced in some ATL patients following allo-HSCT. To further analyze HTLV-1-specific CD4(+) T cell responses, we identified a novel HLA-DRB1*0101-restricted epitope, Tax155-167, recognized by HTLV-1-specific CD4(+) Th1-like cells, a major population of HTLV-1-specific CD4(+) T cell line, which was established from an ATL patient at 180 d after allo-HSCT from an unrelated seronegative donor by in vitro stimulation with HTLV-1-infected cells from the same patient. Costimulation of PBMCs with both the identified epitope (Tax155-167) and known CTL epitope peptides markedly enhanced the expansion of Tax-specific CD8(+) T cells in PBMCs compared with stimulation with CTL epitope peptide alone in all three HLA-DRB1*0101(+) patients post-allo-HSCT tested. In addition, direct detection using newly generated HLA-DRB1*0101/Tax155-167 tetramers revealed that Tax155-167-specific CD4(+) T cells were present in all HTLV-1-infected individuals tested, regardless of HSCT. These results suggest that Tax155-167 may be the dominant epitope recognized by HTLV-1-specific CD4(+) T cells in HLA-DRB1*0101(+)-infected individuals and that Tax-specific CD4(+) T cells may augment the graft-versus-Tax effects via efficient induction of Tax-specific CD8(+) T cell responses.
Affiliations:Department of Immunotherapeutics, Tokyo Medical and Dental University, Tokyo 113-8519, Japan.
Reference Type:Literature
PubMed ID:23475215
Journal:J Immunol
Journal Volume:190
Article Pages:4382-92
Journal ISSN:0022-1767
Article Chemical List:Epitopes, T-Lymphocyte;Gene Products, tax;tax protein, Human T-lymphotrophic virus 1
Article MeSH List:Aged; CD4-Positive T-Lymphocytes(immunology; metabolism; transplantation); Epitopes, T-Lymphocyte(immunology); Female; Gene Products, tax(administration & dosage; immunology); Graft vs Leukemia Effect(immunology); Hematopoietic Stem Cell Transplantation(methods); Human T-lymphotropic virus 1(immunology); Humans; Leukemia-Lymphoma, Adult T-Cell(immunology; surgery); Male; Middle Aged; Transplantation, Homologous
Curation Last Updated:2014-10-03 22:52:55