Human T-cell leukemia virus type-I (HTLV-I)-specific T-cell responses detected using three-divided glutathione-S-transferase (GST)-Tax fusion proteins

Kurihara, Ken; Shimizu, Yukiko; Takamori, Ayako; Harashima, Nanae; Noji, Misato; Masuda, Tohru; Utsunomiya, Atae; Okamura, Jun; Kannagi, Mari

doi:10.1016/j.jim.2006.03.013

Cited by 7 publications

(9 citation statements)

References 32 publications

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“…Although ATL patients maintain antibodies against various viral products in their serum, HTLV-1 expression in ATL cells immediately after isolation from patients is very low and becomes significantly induced after culture for several hours in vitro (10,18,31). This phenomenon is observed in T cells from not only ATL patients but also HAM/ TSP patients and asymptomatic HTLV-1 carriers (1,8,17), indicating that there may be a common mechanism for transient suppression of HTLV-1 expression in vivo.…”

mentioning

confidence: 99%

Stromal Cell-Mediated Suppression of Human T-Cell Leukemia Virus Type 1 Expression In Vitro and In Vivo by Type I Interferon

Kinpara

Hasegawa

Utsunomiya

et al. 2009

J Virol

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mentioning

confidence: 99%

Stromal Cell-Mediated Suppression of Human T-Cell Leukemia Virus Type 1 Expression In Vitro and In Vivo by Type I Interferon

Kinpara

Hasegawa

Utsunomiya

et al. 2009

J Virol

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“…The GST-Tax fusion protein-based assay can detect both CD4 + and CD8 + T cell responses, irrespective of HLA types. However, this sensitivity is not as good as single-cell analysis by flow cytometry (31). As shown in Fig.…”

Section: Resultsmentioning

confidence: 91%

“…As shown in Fig. 3A, the T4 cells produced significantly higher amounts of IFN-g in response to GST-TaxABC and GST-Tax-B (residues 113-237) (31) but not GST-Tax-A (residues 1-127) (31) and -C (residues 224-353 (31), when compared with the GST control protein, indicating that the T4 cells recognized the central region (residues 113-237) of the Tax Ag. We next synthesized eight overlapping 25-mer peptides spanning the central region of Tax (residues 103-246) and analyzed their abilities to stimulate T4 cells (Table II).…”

Section: Determination Of the Minimum Epitope Recognized By T4 Cellsmentioning

confidence: 86%

“…HTLV-1 Tax-specific T cell responses were evaluated using GST-fusion proteins of the N-terminal (residues 1-127), central (residues 113-237), and C-terminal (residues 224-353) regions of HTLV-1 Tax (GST-Tax-A, -B, and -C, respectively) as described previously (13,31). PBMCs (1 3 10 6 cells/ml) were incubated with or without a mixture of GST-Tax-A, -B, and -C proteins (GST-TaxABC) in 200 ml RPMI 1640 medium supplemented with 10% FCS.…”

Section: Gst-tax Fusion Protein-based Immunoassaymentioning

confidence: 99%

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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

Tamai

Hasegawa

Takamori

et al. 2013

The Journal of Immunology

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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.

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“…A number of epitopes of Tax, the major HTLV-1 oncogenic transactivator protein, have been recognized by HTLV-1-specific CD8 + CTLs in infected individuals carrying HLA-A2, -A11, or -A24 [4–10]. In HLA-A2 + patients, the frequency of Tax-specific CTLs can be as high as 30% of all CD8 + T-cells in the peripheral blood [11] and even higher in CSF[4, 12, 13], with Tax(11-19) epitope being the immunodominant epitope in both asymptomatic carriers [14], ATL [7, 15], and HAM [4, 6, 12, 16–19]. During the development of ATL, general immune suppression has been reportedly due to dysfunction of Tax-specific CTLs [7, 20].…”

Section: Introductionmentioning

confidence: 99%

In vivo immunogenicity of Tax(11–19) epitope in HLA-A2/DTR transgenic mice: Implication for dendritic cell-based anti-HTLV-1 vaccine

Sagar

Masih

Schell

et al. 2014

Vaccine

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Viral oncoprotein Tax plays key roles in transformation of human T-cell leukemia virus (HTLV-1)-infected T cells leading to adult T-cell leukemia (ATL), and is the key antigen recognized during HTLV-associated myelopathy (HAM). In HLA-A2+ asymptomatic carriers as well as ATL and HAM patients, Tax(11-19) epitope exhibits immunodominance. Here, we evaluate CD8 T-cell immune response against this epitope in the presence and absence of dendritic cells (DCs) given the recent encouraging observations made with Phase 1 DC-based vaccine trial for ATL. To facilitate these studies, we first generated an HLA-A2/DTR hybrid mouse strain carrying the HLA-A2.1 and CD11c-DTR genes. We then studied CD8 T-cell immune response against Tax(11-19) epitope delivered in the absence or presence of Freund’s adjuvant and/or DCs. Overall results demonstrate that naturally presented Tax epitope could initiate an antigen-specific CD8 T cell response in vivo but failed to do so upon DC depletion. Presence of adjuvant potentiated Tax(11-19)-specific response. Elevated serum IL-6 levels coincided with depletion of DCs whereas decreased TGF-β was associated with adjuvant use. Thus, Tax(11-19) epitope is a potential candidate for the DC-based anti-HTLV-1 vaccine and the newly hybrid mouse strain could be used for investigating DC involvement in human class-I-restricted immune responses.

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Human T-cell leukemia virus type-I (HTLV-I)-specific T-cell responses detected using three-divided glutathione-S-transferase (GST)-Tax fusion proteins

Cited by 7 publications

References 32 publications

Stromal Cell-Mediated Suppression of Human T-Cell Leukemia Virus Type 1 Expression In Vitro and In Vivo by Type I Interferon

Stromal Cell-Mediated Suppression of Human T-Cell Leukemia Virus Type 1 Expression In Vitro and In Vivo by Type I Interferon

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

In vivo immunogenicity of Tax(11–19) epitope in HLA-A2/DTR transgenic mice: Implication for dendritic cell-based anti-HTLV-1 vaccine

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