scholarly journals Early gene m18, a novel player in the immune response to murine cytomegalovirus

2002 ◽  
Vol 83 (2) ◽  
pp. 311-316 ◽  
Author(s):  
Rafaela Holtappels ◽  
Natascha K. A. Grzimek ◽  
Doris Thomas ◽  
Matthias J. Reddehase
Keyword(s):  
T Cell ◽  
Immune Evasion ◽  
Antigen Processing ◽  
Computational Prediction ◽  
T Cell Response ◽  
Early Gene ◽  
Murine Cytomegalovirus ◽  
Current Evidence ◽  
Antigenic Peptides ◽  
E Proteins

The identification of all antigenic peptides encoded by a pathogen, its T cell ‘immunome’, is a research aim for rational vaccine design. Screening of proteome-spanning peptide libraries or computational prediction is used to identify antigenic peptides recognized by CD8 T cells. Based on their high coding capacity, cytomegaloviruses (CMVs) could specify numerous antigenic peptides. Yet, current evidence indicates that the memory CD8 T cell response in a given haplotype is actually focused on a few viral proteins. CMVs actively interfere with antigen processing and presentation by the expression of immune evasion proteins. In the case of murine CMV (mCMV), these proteins are effectual in the early (E) phase of the virus replication cycle and should thus preclude the presentation of peptides derived from E proteins. Notably, the m18 gene is here added to a growing list of mCMV E genes that encode antigenic peptides in spite of the E phase immune evasion strategies of the virus.

scholarly journals Identification of a Kd-restricted antigenic peptide encoded by murine cytomegalovirus early gene M84

2000 ◽  
Vol 81 (12) ◽  
pp. 3037-3042 ◽  
Author(s):  
Rafaela Holtappels ◽  
Doris Thomas ◽  
Matthias J. Reddehase
Keyword(s):  
Immune Evasion ◽  
Antigen Processing ◽  
Matrix Protein ◽  
Early Gene ◽  
Antigenic Peptide ◽  
Murine Cytomegalovirus ◽  
Class I Mhc ◽  
Mhc I ◽  
Cmv Matrix ◽  
Phase Protein

The two sister cytomegaloviruses (CMVs), human and murine CMV, have both evolved immune evasion functions that interfere with the major histocompatibility complex class I (MHC-I) pathway of antigen processing and presentation and are effectual in the early (E) phase of virus gene expression. However, studies on murine CMV have shown that E-phase immune evasion is leaky. An E-phase protein involved in immune evasion, namely m04-gp34, was found to simultaneously account for an antigenic peptide presented by the MHC-I molecule Dd. Recent work has demonstrated the induction of protective immunity specific for the E-phase protein M84-p65, one of two murine CMV homologues of the human CMV matrix protein UL83-pp65. In this study, the identification of the MHC-I Kd-restricted M84 peptide 297AYAGLFTPL305 is documented. This peptide is the third antigenic peptide described for murine CMV and the second that escapes immunosubversive mechanisms.

scholarly journals Uncovering the Tumor Antigen Landscape: What to Know about the Discovery Process

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1660
Author(s):  
Sara Feola ◽  
Jacopo Chiaro ◽  
Beatriz Martins ◽  
Vincenzo Cerullo
Keyword(s):  
T Cell ◽  
Cancer Immunotherapy ◽  
Tumor Antigens ◽  
T Cell Response ◽  
Antigenic Peptides ◽  
T Cell Epitopes ◽  
Antigen Discovery ◽  
Future Challenges ◽  
Major Bottleneck ◽  
Therapeutic Cancer Vaccines

According to the latest available data, cancer is the second leading cause of death, highlighting the need for novel cancer therapeutic approaches. In this context, immunotherapy is emerging as a reliable first-line treatment for many cancers, particularly metastatic melanoma. Indeed, cancer immunotherapy has attracted great interest following the recent clinical approval of antibodies targeting immune checkpoint molecules, such as PD-1, PD-L1, and CTLA-4, that release the brakes of the immune system, thus reviving a field otherwise poorly explored. Cancer immunotherapy mainly relies on the generation and stimulation of cytotoxic CD8 T lymphocytes (CTLs) within the tumor microenvironment (TME), priming T cells and establishing efficient and durable anti-tumor immunity. Therefore, there is a clear need to define and identify immunogenic T cell epitopes to use in therapeutic cancer vaccines. Naturally presented antigens in the human leucocyte antigen-1 (HLA-I) complex on the tumor surface are the main protagonists in evocating a specific anti-tumor CD8+ T cell response. However, the methodologies for their identification have been a major bottleneck for their reliable characterization. Consequently, the field of antigen discovery has yet to improve. The current review is intended to define what are today known as tumor antigens, with a main focus on CTL antigenic peptides. We also review the techniques developed and employed to date for antigen discovery, exploring both the direct elution of HLA-I peptides and the in silico prediction of epitopes. Finally, the last part of the review analyses the future challenges and direction of the antigen discovery field.

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.  

scholarly journals Design of an epitope-based peptide vaccine against the SARS-CoV-2: a vaccine-informatics approach

2020 ◽  
Author(s):  
Aftab Alam ◽  
Arbaaz Khan ◽  
Nikhat Imam ◽  
Mohd Faizan Siddiqui ◽  
Mohd Waseem ◽  
...  
Keyword(s):  
T Cell ◽  
Vaccine Development ◽  
Peptide Vaccine ◽  
Specific Treatment ◽  
T Cell Response ◽  
Surface Glycoprotein ◽  
Antigenic Peptides ◽  
Population Coverage ◽  
Geographical Regions ◽  
Cluster Of Differentiation

Abstract The recurrent and recent global outbreak of the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has turned into a global concern which has infected more than 42 million people all over the globe, and this number is increasing in hours. Unfortunately, no vaccine or specific treatment is available, which makes it more deadly. A vaccine-informatics approach has shown significant breakthrough in peptide-based epitope mapping and opens the new horizon in vaccine development. In this study, we have identified a total of 15 antigenic peptides [including thymus cells (T-cells) and bone marrow or bursa-derived cells] in the surface glycoprotein (SG) of SARS-CoV-2 which is nontoxic and nonallergenic in nature, nonallergenic, highly antigenic and non-mutated in other SARS-CoV-2 virus strains. The population coverage analysis has found that cluster of differentiation 4 (CD4+) T-cell peptides showed higher cumulative population coverage over cluster of differentiation 8 (CD8+) peptides in the 16 different geographical regions of the world. We identified 12 peptides ((LTDEMIAQY, WTAGAAAYY, WMESEFRVY, IRASANLAA, FGAISSVLN, VKQLSSNFG, FAMQMAYRF, FGAGAALQI, YGFQPTNGVGYQ, LPDPSKPSKR, QTQTNSPRRARS and VITPGTNTSN) that are $80\hbox{--} 90\%$ identical with experimentally determined epitopes of SARS-CoV, and this will likely be beneficial for a quick progression of the vaccine design. Moreover, docking analysis suggested that the identified peptides are tightly bound in the groove of human leukocyte antigen molecules which can induce the T-cell response. Overall, this study allows us to determine potent peptide antigen targets in the SG on intuitive grounds, which opens up a new horizon in the coronavirus disease (COVID-19) research. However, this study needs experimental validation by in vitro and in vivo.

scholarly journals Chimeric Yellow Fever/Dengue Virus as a Candidate Dengue Vaccine: Quantitation of the Dengue Virus-Specific CD8 T-Cell Response

2000 ◽  
Vol 74 (17) ◽  
pp. 8094-8101 ◽  
Author(s):  
Robbert G. van der Most ◽  
Kaja Murali-Krishna ◽  
Rafi Ahmed ◽  
James H. Strauss
Keyword(s):  
T Cells ◽  
T Cell ◽  
Dengue Virus ◽  
Yellow Fever ◽  
Cd8 T Cells ◽  
Cell Response ◽  
Protective Efficacy ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
E Proteins

ABSTRACT We have constructed a chimeric yellow fever/dengue (YF/DEN) virus, which expresses the premembrane (prM) and envelope (E) genes from DEN type 2 (DEN-2) virus in a YF virus (YFV-17D) genetic background. Immunization of BALB/c mice with this chimeric virus induced a CD8 T-cell response specific for the DEN-2 virus prM and E proteins. This response protected YF/DEN virus-immunized mice against lethal dengue encephalitis. Control mice immunized with the parental YFV-17D were not protected against DEN-2 virus challenge, indicating that protection was mediated by the DEN-2 virus prM- and E-specific immune responses. YF/DEN vaccine-primed CD8 T cells expanded and were efficiently recruited into the central nervous systems of DEN-2 virus challenged mice. At 5 days after challenge, 3 to 4% of CD8 T cells in the spleen were specific for the prM and E proteins, and 34% of CD8 T cells in the central nervous system recognized these proteins. Depletion of either CD4 or CD8 T cells, or both, strongly reduced the protective efficacy of the YF/DEN virus, stressing the key role of the antiviral T-cell response.

scholarly journals Archaeosome Adjuvant Overcomes Tolerance to Tumor-Associated Melanoma Antigens Inducing Protective CD8+T Cell Responses

2010 ◽  
Vol 2010 ◽  
pp. 1-13 ◽  
Author(s):  
Lakshmi Krishnan ◽  
Lise Deschatelets ◽  
Felicity C. Stark ◽  
Komal Gurnani ◽  
G. Dennis Sprott
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Regulatory Cells ◽  
T Cell Responses ◽  
T Cell Response ◽  
Antigen Delivery ◽  
Antigenic Peptides ◽  
Cell Responses ◽  
Tumor Protection ◽  
Melanoma Antigens

Vesicles comprised of the ether glycerolipids of the archaeonMethanobrevibacter smithii(archaeosomes) are potent adjuvants for evoking CD8+T cell responses. We therefore explored the ability of archaeosomes to overcome immunologic tolerance to self-antigens. Priming and boosting of mice with archaeosome-antigen evoked comparable CD8+T cell response and tumor protection to an alternate boosting strategy utilizing live bacterial vectors for antigen delivery. Vaccination with melanoma antigenic peptides TRP181-189and Gp10025-33delivered in archaeosomes resulted in IFN-γproducing antigen-specific CD8+T cells with strong cytolytic capability and protection against subcutaneous B16 melanoma. Targeting responses against multiple antigens afforded prolonged median survival against melanoma challenge. Entrapment of multiple peptides within the same vesicle or admixed formulations were both effective at evoking CD8+T cells against each antigen. Melanoma-antigen archaeosome formulations also afforded therapeutic protection against established B16 tumors when combined with depletion of T-regulatory cells. Overall, we demonstrate that archaeosome adjuvants constitute an effective choice for formulating cancer vaccines.

Loss of EBV-Specific CD4+T Cells during Progression to EBV-Related AIDS Non-Hodgkin Lymphoma: Restoration by Highly Active Antiretroviral Therapy (HAART).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3110-3110
Author(s):  
Erwan R. Piriou ◽  
Christine Jansen ◽  
Karel van Dort ◽  
Iris De Cuyper ◽  
Nening M. Nanlohy ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Response ◽  
Cd4 T Cells ◽  
Antigen Processing ◽  
Ex Vivo ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
Cell Numbers

Abstract Objective: EBV-specific CD8+ T cells have been extensively studied in various settings, and appear to play a major role in the control of EBV-related malignancies. In contrast, it is still unclear whether EBV-specific CD4+ T cells play a role in vivo. To study this question, an assay was developed to measure the CD4+ T-cell response towards two EBV antigens, in both healthy (n=14) and HIV-infected subjects (n=23). In addition, both HAART-treated (n=12) and untreated HIV+ individuals (n=14) - including progressors to EBV-related lymphoma - were studied longitudinally. Methods: EBV-specific CD4+ T cells were stimulated with peptide pools from latent protein EBNA1 and lytic protein BZLF1, and detected by measurement of IFNg-production. Results: After direct ex vivo stimulation, EBNA1 or BZLF1-specific IFNg- (and/or IL2) producing CD4+ T cell numbers were low, and measurable in less than half of the subjects studied (either HIV- and HIV+). Therefore, PBMC were cultured for 12 days in the presence of peptides and IL2 (from day 3), and then restimulated with peptides, allowing specific and reproducible expansion of EBV-specific CD4+ T cells, independent of HLA type and ex vivo antigen processing. Interestingly, numbers of EBV-specific CD4+ T cells inversely correlated with EBV viral load, implying an important role for EBV-specific CD4+ T cells in the control of EBV in vivo. Untreated HIV-infected individuals had a lower CD4+ T cell response to EBNA1 and BZLF1 as compared to healthy EBV carriers and HAART-treated HIV+ subjects. In longitudinal samples, EBNA1-specific, but not BZLF1-specific T-cell numbers increased after HAART, while EBV load was not affected by treatment. In all the progressors to EBV-related lymphoma, EBV-specific CD4+ T cells were lost at least 24 months before lymphoma diagnosis. Conclusions: Both cross-sectional and longitudinal data suggest an important role for EBV-specific CD4+ T cells in the control of EBV-related malignancies. Furthermore, it seems that HAART treatment leads to recovery of EBNA1-specific, but not BZLF1-specific CD4+ T-cell responses, implying changes in the latency pattern of EBV, despite an unaltered cell-associated EBV DNA load. Thus, early HAART treatment might prevent loss of specific CD4+ T-cell help and progression to NHL.

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