scholarly journals Protective CD8+ T-cell response against Hantaan virus infection induced by immunization with designed linear multi-epitope peptides in HLA-A2.1/Kb transgenic mice

2020 ◽  
Vol 17 (1) ◽  
Author(s):  
Ying Ma ◽  
Kang Tang ◽  
Yusi Zhang ◽  
Chunmei Zhang ◽  
Linfeng Cheng ◽  
...  
Keyword(s):  
T Cell ◽  
Transgenic Mice ◽  
Challenge Test ◽  
T Cell Response ◽  
Hantaan Virus ◽  
Cytotoxic T Cell ◽  
Epitope Peptide ◽  
Ctl Epitope ◽  
Ifn Γ ◽  
Hla A2.1

Abstract Background An effective vaccine that prevents disease caused by hantaviruses is a global public health priority, but up to now, no vaccine has been approved for worldwide use. Therefore, novel vaccines with high prophylaxis efficacy are urgently needed. Methods Herein, we designed and synthesized Hantaan virus (HTNV) linear multi-epitope peptide consisting of HLA-A*02-restricted HTNV cytotoxic T cell (CTL) epitope and pan HLA-DR-binding epitope (PADRE), and evaluated the immunogenicity, as well as effectiveness, of multi-epitope peptides in HLA-A2.1/Kb transgenic mice with interferon (IFN)-γ enzyme-linked immunospot assay, cytotoxic mediator detection, proliferation assay and HTNV-challenge test. Results The results showed that a much higher frequency of specific IFN-γ-secreting CTLs, high levels of granzyme B production, and a strong proliferation capacity of specific CTLs were observed in splenocytes of mice immunized with multi-epitope peptide than in those of a single CTL epitope. Moreover, pre-immunization of multi-epitope peptide could reduce the levels of HTNV RNA loads in the liver, spleen and kidneys of mice, indicating that specific CTL responses induced by multi-epitope peptide could reduce HTNV RNA loads in vivo. Conclusions This study may provide an important foundation for the development of novel peptide vaccines for HTNV prophylaxis.

scholarly journals Protective CD8+ T-cell response against Hantaan virus infection induced by immunization with designed linear multi-epitope peptides in HLA-A2.1/Kb transgenic mice

2020 ◽  
Author(s):  
Ying Ma ◽  
Kang Tang ◽  
Yusi Zhang ◽  
Chunmei Zhang ◽  
Linfeng Cheng ◽  
...  
Keyword(s):  
T Cell ◽  
Transgenic Mice ◽  
Challenge Test ◽  
T Cell Response ◽  
Hantaan Virus ◽  
Cytotoxic T Cell ◽  
Epitope Peptide ◽  
Ctl Epitope ◽  
Ifn Γ ◽  
Hla A2.1

Abstract Background: An effective vaccine that prevents disease caused by hantaviruses is a global public health priority, but up to now, no vaccine has been approved for worldwide use. Therefore, novel vaccines with high prophylaxis efficacy are urgently needed.Methods: Herein, we designed and synthesized Hantaan virus (HTNV) linear multi-epitope peptide consisting of HLA-A*02-restricted HTNV cytotoxic T cell (CTL) epitope and pan HLA-DR-binding epitope (PADRE), and evaluated the immunogenicity, as well as effectiveness, of multi-epitope peptides in HLA-A2.1/Kb transgenic mice with interferon (IFN)-γ enzyme-linked immunospot assay, cytotoxic mediator detection, proliferation assay and HTNV-challenge test.Results: The results showed that a much higher frequency of specific IFN-γ-secreting CTLs, high levels of granzyme B production, and a strong proliferation capacity of specific CTLs were observed in splenocytes of mice immunized with multi-epitope peptide than in those of a single CTL epitope. Moreover, pre-immunization of multi-epitope peptide could reduce the levels of HTNV RNA loads in the liver, spleen and kidneys of mice, indicating that specific CTL responses induced by multi-epitope peptide could reduce HTNV RNA loads in vivo.Conclusions: This study may provide an important foundation for the development of novel peptide vaccines for HTNV prophylaxis.

scholarly journals Protective CD8+ T-cell response against Hantaan virus infection induced by immunization with designed linear multi-epitope peptides in HLA-A2.1/Kb transgenic mice

2020 ◽  
Author(s):  
Ying Ma ◽  
Kang Tang ◽  
Yusi Zhang ◽  
Chunmei Zhang ◽  
Linfeng Cheng ◽  
...  
Keyword(s):  
T Cell ◽  
Transgenic Mice ◽  
Challenge Test ◽  
T Cell Response ◽  
Hantaan Virus ◽  
Cytotoxic T Cell ◽  
Epitope Peptide ◽  
Ctl Epitope ◽  
Ifn Γ ◽  
Hla A2.1

Abstract Background: An effective vaccine that prevents disease caused by hantaviruses is a global public health priority, but up to now, no vaccine has been approved for worldwide use. Therefore, novel vaccines with high prophylaxis efficacy are urgently needed.Methods: Herein, we designed and synthesized Hantaan virus (HTNV) linear multi-epitope peptide consisting of HLA-A*02-restricted HTNV cytotoxic T cell (CTL) epitope and pan HLA-DR-binding epitope (PADRE), and evaluated the immunogenicity, as well as effectiveness, of multi-epitope peptides in HLA-A2.1/Kb transgenic mice with interferon (IFN)-γ enzyme-linked immunospot assay, cytotoxic mediator detection, proliferation assay and HTNV-challenge test.Results: The results showed that a much higher frequency of specific IFN-γ-secreting CTLs, high levels of granzyme B production, and a strong proliferation capacity of specific CTLs were observed in splenocytes of mice immunized with multi-epitope peptide than in those of a single CTL epitope. Moreover, pre-immunization of multi-epitope peptide could reduce the levels of HTNV RNA loads in the liver, spleen and kidneys of mice, indicating that specific CTL responses induced by multi-epitope peptide could reduce HTNV RNA loads in vivo.Conclusions: This study may provide an important foundation for the development of novel peptide vaccines for HTNV prophylaxis.

scholarly journals Protective CD8+ T-cell response against Hantaan virus infection induced by immunization with designed linear multi-epitope peptides in HLA-A2.1/Kb transgenic mice

2020 ◽  
Author(s):  
Ying Ma ◽  
Kang Tang ◽  
Yusi Zhang ◽  
Chunmei Zhang ◽  
Linfeng Cheng ◽  
...  
Keyword(s):  
T Cell ◽  
Transgenic Mice ◽  
T Cell Response ◽  
Hantaan Virus ◽  
Cytotoxic T Cell ◽  
Effective Vaccine ◽  
Epitope Peptide ◽  
Ctl Epitope ◽  
Ifn Γ ◽  
Hla A2.1

Abstract Background An effective vaccine that prevents disease caused by hantaviruses is a global public health priority, but up to now, no vaccine has been approved for worldwide use. Therefore, novel vaccines with high prophylaxis efficacy are urgently needed.Methods Herein, we designed and synthesized Hantaan virus (HTNV) linear multi-epitope peptide consisting of HLA-A*02-restricted HTNV cytotoxic T cell (CTL) epitope and pan HLA-DR-binding epitope (PADRE), and evaluated the immunogenicity, as well as effectiveness, of multi-epitope peptides in HLA-A2.1/Kb transgenic mice with interferon (IFN)-γ enzyme-linked immunospot assay, cytotoxic mediator detection, proliferation assay and HTNV-challenge test.Results The results showed that a much higher frequency of specific IFN-γ-secreting CTLs, high levels of granzyme B production, and a strong proliferation capacity of specific CTLs were observed in splenocytes of mice immunized with multi-epitope peptide than in those of a single CTL epitope. Moreover, pre-immunization of multi-epitope peptide could reduce the levels of HTNV RNA loads in the liver, spleen and kidneys of mice, indicating that specific CTL responses induced by multi-epitope peptide could inhibit HTNV replication in vivo.Conclusions This study may provide an important foundation for the development of novel peptide vaccines for HTNV prophylaxis.

scholarly journals TLR agonists activate HPV11 E7-pulsed DCs to promote a specific T cell response in a murine model

2011 ◽  
Vol 56 (No. 12) ◽  
pp. 602-611 ◽  
Author(s):  
XH Mao ◽  
XZ Chen ◽  
WW Zhang ◽  
JY Wang ◽  
LF Liu ◽  
...  
Keyword(s):  
T Cell ◽  
Mouse Model ◽  
Cytokine Production ◽  
T Cell Response ◽  
Antigenic Peptides ◽  
Epitope Peptide ◽  
Tlr Agonists ◽  
Ctl Epitope ◽  
Th1 Cytokine

: Some TLR agonists may up-regulate the activation of dendritic cells caused by viral antigenic peptides and antigen-specific cytotoxic T lymphocytes, which are crucial in HPV vaccine development. We investigated the ability of three TLR agonists, imiquimod, PIC and CpG, to stimulate the maturation of murine BM-DCs loaded with HPV11E7 CTL epitopes, and the subsequent effect on HPV-specific T cell responses and tumour protection in a C57BL/6 mouse model. We found that TLR agonists, mostly PIC and imiquimod, stimulated the maturation of BM-DCs pulsed with HPV11E7 CTL epitope peptide. In combination with the epitope peptide, the TLR agonists CPG and PIC augmented epitope-specific Th1 cytokine production in vivo, while imiquimod and CPG, but not PIC, enhanced Th1 cytokine production in vitro. However, we failed to observe in vivo CTL cytotoxicity and anti-tumour protection upon TLR ligation in our mouse model. Our results demonstrate that TLR agonists activate HPV11E7 CTL epitope pulsed BM-DCs to promote specific Th1 immunity in C57BL/6 mouse model, indicating the promise of TLR agonists as adjuvants for HPV epitope/DC-based multifaceted vaccines against HPV infections such as condyloma accuminatum.  

CD4 T-Helper Responses to the ALK Protein in Patients with ALK-Positive ALCL.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3352-3352
Author(s):  
Kamel K. Ait-Tahar ◽  
Chris S.R. Hatton ◽  
Karen K. Pulford
Keyword(s):  
T Cell ◽  
T Cell Response ◽  
Cytotoxic T Cell ◽  
Immune Recognition ◽  
T Helper ◽  
Healthy Donors ◽  
Irrelevant Peptide ◽  
Ifn Γ ◽  
Alk Positive ◽  
Alk Protein

Abstract Anaplstic Lymphoma Kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) has a favourable prognostic outlook compared to ALK-negative AlCL, possibly as a result of the immune recognition of the ALK protein. We have previously shown the presence of both a cytotoxic T cell and an antibody response to the ALK protein in patients with ALK-positive ALCL. The aim of our present study was to investigate the presence of a CD4 T-helper (Th) response in patients with ALK-positive ALCL and in control individuals. Using the TEPITOPE web-based predicitive search algorithm, three 24-mer promiscuous peptides were identified from the ALK sequence as being potentially immunogenic in the context of MHC class II. A gamma-interferon (γ-IFN) and IL-4 ELISPOT assay was used to detect a T cell response in the peripheral blood cells from patients with ALK-positive and ALK- negative ALCL, as well as healthy controls after 6–11 days of culture with the three peptides. ALK278–301 and ALK233–256 were shown to be highly immunogenic in the majority of the ALK-positive patients (see Table). ALK411–434 was immunogenic to T cells from only one of the ALK-positive patients (Patient 4). Cells from none of the two ALK-negative ALCL patients or the five healthy donors showed any reactivity to the ALK peptides. No response to the control irrelevant peptide was observed in any of the ALCL patients or healthy donors. With the exception of one ALK-positive ALCL patient (Patient 2), no significant IL-4 response was recorded in any of the patients or controls. All of the ALK-positive patients presented antibodies to the ALK protein at time of diagnosis.These findings further demonstrate the immunogenicity of the ALK protein and are suggestive of a Th1 type of immune response to the protein. Our findings are of potential prognostic value and open up therapeutic options for those ALK-positive patients who do not respond well to chemotherapy. Summary of the CD4 Th responses to ALK in ALCL patients and healthy donors None PHA (10 μ g/ml) ALK233–256 (10 μM)- (IFN- γ/IL-4) ALK278–301(10 μM)- (IFN- γ/IL-4) ALK411–434 (10 μM)- (IFN- γ/IL-4) Irrelevant peptide (10 μM)- (IFN- γ) Antibody titres to ALK (IgG isotype) ND= Not done. Results are of triplicate cultures ALK+ve patients Patient 1 12 188 56/10 44/18 22/6 8 1/2250 Patient 2 20 240 126/48 78/52 40/26 18 1/2250 Patient 3 14 48 38/ND 24/ND 12/ND 16 1/6750 Patient 4 6 108 64/8 72/8 22/6 10 1/60750 Patient 5 10 48 36/13 26/18 12/12 14 1/6750 Patient 6 15 132 74/ND 58/ND 28/ND 18 1/6750 Patient 7 10 180 34/28 56/32 12/9 12 1/750 ALK-ve patients Patient 8 14 122 12/10 10/6 12/14 22 −ve Patient 9 16 82 14/ND 12/ND 10/ND 24 −ve Healthy Donors Normal 1 22 148 18/14 22/24 26/12 10 −ve Normal 2 12 18 2/4 6/8 12/2 4 −ve Normal 3 10 38 12/10 12/16 9/4 18 −ve Normal 4 9 172 9/ND 10/ND 6/ND 12 −ve Normal 5 4 108 8/12 8/12 2/1 10 −ve

Evaluation of HTLV-1 Cytotoxic T-Cell Epitopes in HLA-A2.1 Transgenic Mice

2001 ◽  
pp. 1008-1009
Author(s):  
Roshni Sundaram ◽  
Christopher M. Walker ◽  
Pravin T. P. Kaumaya
Keyword(s):  
T Cell ◽  
Transgenic Mice ◽  
Cytotoxic T Cell ◽  
T Cell Epitopes ◽  
Hla A2.1

Cytotoxic T Cell Responses Against Human Class I Molecules in Normal and HLA-A2.1 Transgenic Mice

1990 ◽  
pp. 179-190 ◽  
Author(s):  
V. H. Engelhard ◽  
E. J. Bernhard ◽  
M. J. Holterman ◽  
A.-X. T. Le ◽  
R. Henderson ◽  
...  
Keyword(s):  
T Cell ◽  
Transgenic Mice ◽  
T Cell Responses ◽  
Class I ◽  
Cytotoxic T Cell ◽  
Human Class ◽  
Cell Responses ◽  
Cytotoxic T Cell Responses ◽  
Hla A2.1

scholarly journals TL antigen as a transplantation antigen recognized by TL-restricted cytotoxic T cells.

1994 ◽  
Vol 179 (3) ◽  
pp. 777-784 ◽  
Author(s):  
A Morita ◽  
T Takahashi ◽  
E Stockert ◽  
E Nakayama ◽  
T Tsuji ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Transgenic Mice ◽  
Tumor Antigens ◽  
Cytotoxic T Cells ◽  
T Cell Response ◽  
Class I ◽  
Cytotoxic T Cell ◽  
Transplantation Antigen ◽  
Classical Class

In contrast to broadly expressed classical class I antigens of the major histocompatibility complex, structurally closely related TL antigens are expressed in a highly restricted fashion. Unlike classical class I antigens, TL antigens are not known to be targets of cytotoxic T cells or to mediate graft rejection. Whereas classical class I antigens function as antigen-presenting molecules to T cell receptors (TCR), the role of TL is yet to be defined. To elucidate the function of TL, we have derived transgenic mice expressing TL in most tissues including skin by introducing a TL gene, T3b of C57BL/6 mouse origin, driven by the H-2Kb promoter. By grafting the skin of transgenic mice, we demonstrate that TL can serve as a transplantation antigen and mediate a TCR-alpha/beta+ CD8+ cytotoxic T cell response. This T cell recognition of TL does not require antigen presentation by H-2 molecules. Furthermore, we show that C57BL/6 F1 mice develop CD8+ T cells that are cytotoxic for C57BL/6 TL+ leukemia cells, providing further support for the concept that aberrantly expressed nonmutated proteins such as TL can be recognized as tumor antigens.

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