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Immunodominant T cell

Corinna La Rosa, Jeff Longmate, Joy Martinez, Qiao Zhou, Teodora I Kaltcheva, Weimin Tsai, Jennifer Drake, Mary Carroll, Felix Wussow, Flavia Chiuppesi, Nicola Hardwick, Sanjeet Dadwal, Ibrahim Aldoss, Ryotaro Nakamura, John A Zaia, Don J Diamond
Attenuated poxvirus Modified vaccinia Ankara (MVA) is a useful viral-based vaccine for clinical investigation, because of its excellent safety profile and property of inducing potent immune responses against recombinant (r) antigens. We developed Triplex by constructing an rMVA encoding three immunodominant CMV antigens which stimulates a host anti-viral response: UL83 (pp65), UL123 (IE1-exon4), and UL122 (IE2-exon5). We completed the first clinical evaluation of the Triplex vaccine in 24 healthy adults, with or without immunity to CMV and vaccinia virus (previous DryVax smallpox vaccination)...
October 19, 2016: Blood
Jong-Chan Youn
Immunosenescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterized by impaired protective immunity and decreased efficacy of vaccines. Immunosenescence affects both the innate and adaptive immune systems; however, the most notable changes are in T cell immunity and include thymic involution, the collapse of T cell receptor (TCR) diversity, an imbalance in T cell populations, and the clonal expansion of senescent T cells. An increasing number of immunological, clinical and epidemiological studies suggest that persistent Cytomegalovirus (CMV) infection is associated with accelerated aging of the immune system and T cell immunosenescence especially...
September 2016: Journal of Hypertension
Xintao Hu, Antonio Valentin, Frances Dayton, Viraj Kulkarni, Candido Alicea, Margherita Rosati, Bhabadeb Chowdhury, Rajeev Gautam, Kate E Broderick, Niranjan Y Sardesai, Malcolm A Martin, James I Mullins, George N Pavlakis, Barbara K Felber
HIV sequence diversity and the propensity of eliciting immunodominant responses targeting variable regions of the HIV proteome are hurdles in the development of an effective AIDS vaccine. An HIV-derived conserved element (CE) p24(gag) plasmid DNA (pDNA) vaccine is able to redirect immunodominant responses to otherwise subdominant and often more vulnerable viral targets. By homology to the HIV immunogen, seven CE were identified in SIV p27(Gag) Analysis of 31 rhesus macaques vaccinated with full-length SIV gag pDNA showed inefficient induction (58% response rate) of cellular responses targeting these CE...
October 12, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Sabine Tischer, René Geyeregger, Julian Kwoczek, Albert Heim, Constanca Figueiredo, Rainer Blasczyk, Britta Maecker-Kolhoff, Britta Eiz-Vesper
BACKGROUND: Human adenovirus (HAdV) infections remain a significant cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Efficient antiviral T-cell responses are necessary to clear infection, which is hampered by delayed immune reconstitution and medical immunosuppression after HSCT. Protective immunity may be conferred by adoptive transfer of HAdV-specific T cells. For identification of patients at risk and monitoring of treatment responses diligent assessment of anti-HAdV cellular immune responses is crucial...
October 7, 2016: Journal of Translational Medicine
Jiju Mani, Lei Wang, Angela G Hückelhoven, Anita Schmitt, Alma Gedvilaite, Nan Jin, Christian Kleist, Anthony D Ho, Michael Schmitt
Human JC and BK polyomaviruses (JCV/BKV) can establish a latent infection without any clinical symptoms in healthy individuals. In immunocompromised hosts infection or reactivation of JCV and BKV can cause lethal progressive multifocal leukoencephalopathy (PML) and hemorrhagic cystitis, respectively. Vaccination with JCV/BKV derived antigen epitope peptides or adoptive transfer of virus-specific T cells would constitute an elegant approach to clear virus-infected cells. Furthermore, donor leukocyte infusion (DLI) is another therapeutic approach which could be helpful for patients with JCV/BKV infections...
October 1, 2016: Oncotarget
Xiaolu Xiong, Jun Jiao, Anthony E Gregory, Pengcheng Wang, Yujing Bi, Xiaoyi Wang, Yongqiang Jiang, Bohai Wen, Daniel A Portnoy, James E Samuel, Chen Chen
Coxiella burnetii is a Gram-negative bacterium that causes acute and chronic Q fever. Due to the severe adverse effect of whole cell vaccination, identification of immunodominant antigens of C. burnetii has become a major focus of Q fever vaccine development. We hypothesized that secreted C. burnetii Type IV secretion system (T4SS) effectors may represent a major class of CD8(+) T cell antigens due to their cytosolic localization. Twenty-nine peptides were identified that elicited robust CD8(+) T cell IFN-γ recall responses from mice infected with C...
October 4, 2016: Journal of Infectious Diseases
Dorothee Kretschmer, Dennis Hanzelmann, Andreas Peschel
Toll-like receptor 2 (TLR2) is regarded as the major innate immunity sensor in infections caused by the Gram-positive bacterial pathogen Staphylococcus aureus. However, previous studies on the roles of TLR2 in S. aureus infections have been elusive and in part contradictory. It has remained particularly unclear if bacterial lipoproteins, the major TLR2 ligands, could serve as antigens with intrinsic adjuvant property for the development of protective vaccines. The study by Vu et al. published in this issue of Proteomics analyzed the antibody and T-cell responses in human sera against major S...
October 2016: Proteomics
Yanhua Wang, Guangxiang Wang, Jian Ping Cai
The study of antigenic epitopes from Toxoplasma gondii has not only enhanced our understanding of the structure and function of antigens, the reactions between antigens and antibodies, and many other aspects of immunology, but it also plays a significant role in the development of new diagnostic reagents and vaccines. In the present study, T. gondii GRA6 epitopes were identified using bioinformatics tools and a synthetic peptide technique. The potential B cell epitopes of GRA6 predicted by bioinformatics tools concentrated upon 3 regions of GRA6, 1-20 aa, 44-103 aa, and 172-221 aa...
August 2016: Korean Journal of Parasitology
Jong-Chan Youn
Immunosenescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterized by impaired protective immunity and decreased efficacy of vaccines. Immunosenescence affects both the innate and adaptive immune systems; however, the most notable changes are in T cell immunity and include thymic involution, the collapse of T cell receptor (TCR) diversity, an imbalance in T cell populations, and the clonal expansion of senescent T cells. An increasing number of immunological, clinical and epidemiological studies suggest that persistent Cytomegalovirus (CMV) infection is associated with accelerated aging of the immune system and T cell immunosenescence especially...
September 2016: Journal of Hypertension
Christopher S Eickhoff, Xiuli Zhang, Jose R Vasconcelos, R Geoffrey Motz, Nicole L Sullivan, Kelly O'Shea, Nicola Pozzi, David W Gohara, Jennifer R Blase, Enrico Di Cera, Daniel F Hoft
Trypanosoma cruzi infection is controlled but not eliminated by host immunity. The T. cruzi trans-sialidase (TS) gene superfamily encodes immunodominant protective antigens, but expression of altered peptide ligands by different TS genes has been hypothesized to promote immunoevasion. We molecularly defined TS epitopes to determine their importance for protection versus parasite persistence. Peptide-pulsed dendritic cell vaccination experiments demonstrated that one pair of immunodominant CD4+ and CD8+ TS peptides alone can induce protective immunity (100% survival post-lethal parasite challenge)...
September 2016: PLoS Pathogens
Cibele M Gaido, Shane Stone, Abha Chopra, Wayne R Thomas, Peter N Le Souëf, Belinda J Hales
: Rhinovirus (RV) species A and C are the most frequent cause of respiratory viral illness worldwide and RV-C has been linked to more severe exacerbations of asthma in young children. Little is known about the immune response against the different RV species, although studies comparing IgG1 antibody titers found impaired antibody responses to RV-C. Therefore, the aim of this study was to assess whether T-cell immunity to RV-C is similarly impaired. We measured T-cell proliferation to overlapping synthetic peptides covering the entire VP1 capsid protein of an RV-A and RV-C genotype for 20 healthy adult donors...
September 14, 2016: Journal of Virology
Luz M Cumba Garcia, April M Huseby Kelcher, Courtney S Malo, Aaron J Johnson
Effective recovery of activated brain infiltrating lymphocytes is critical for investigations involving murine neurological disease models. To optimize lymphocyte recovery, we compared two isolation methods using brains harvested from seven-day Theiler's murine encephalomyelitis virus (TMEV) and TMEV-OVA infected mice. Brains were processed using either a manual dounce based approach or enzymatic digestion using type IV collagenase. The resulting cell suspensions from these two techniques were transferred to a percoll gradient, centrifuged, and lymphocytes were recovered...
September 10, 2016: Journal of Immunological Methods
Cong Yanjun, Zhou Shengyun, Li Linfeng
α-Lactalbumin represents one of the major allergens causing cow milk allergy. Few studies have clearly evaluated immunological relationships between immunoglobulin E (IgE) and immunoglobulin G (IgG)-binding epitopes of α-lactalbumin. IgE- and IgG-binding epitopes were immunolabeled with individual sera from cow milk-allergic patients. Alanine scanning of immunodominant epitopes was used to identify the critical amino acid (aa). Our initial data revealed Val(8) , Phe(9) , Arg(10) , Tyr(103) , Leu(105) , and His(107) were the critical aa for IgE-binding epitope...
October 2016: Journal of Food Science
S T S Chitradevi, G Kaur, U Sivaramakrishna, D Singh, A Bansal
Shigellosis is an acute bacillary diarrheal disease caused by the gram negative bacillus Shigella. The existence of multiple Shigella serotypes and their growing resistance to antibiotics stress the urgent need for the development of vaccine that is protective across all serotypes. Shigella's IpaB antigen is involved in translocon pore formation, promotes bacterial invasion and induces apoptosis in macrophages. S. Typhi GroEL (Hsp 60) is the immunodominant antigen inducing both arms of immunity and has been explored as adjuvant in this study...
October 17, 2016: Vaccine
Fanming Jiang, Xiaoxu Han, Hui Zhang, Bin Zhao, Minghui An, Junjie Xu, Zhenxing Chu, Tao Dong, Hong Shang
BACKGROUND: The purpose of this study was to characterize specific cytotoxic T-cell (CTL) responses in men who have sex with men (MSM) subjects infected with the human immunodeficiency virus type 1 (HIV-1) CRF01_AE subtype during the first year of infection and impacts on viral control and evolution. RESULTS: Fifteen HIV-1 primary infected cases were recruited from Liaoning MSM prospective cohort. CTL responses to Gag, Pol and Nef proteins at 3 month and 1 year post infection were detected with Gamma interferon enzyme-linked immunospot (ELISPOT) assay using optimized consensus overlapping peptides, as well as the viral quasispecies sequences from the synchronous plasma...
2016: BMC Immunology
Jan Petersen, Yvonne Kooy-Winkelaar, Khai Lee Loh, Mai Tran, Jeroen van Bergen, Frits Koning, Jamie Rossjohn, Hugh H Reid
In HLA-DQ8-associated celiac disease, TRAV26-2(+)-TRBV9(+) and TRAV8-3(+)-TRBV6(+) T cells recognize the immunodominant DQ8-glia-α1 epitope, whereupon a non-germline-encoded arginine residue played a key role in binding HLA-DQ8-glia-α1. Whether distinct T cell receptor (TCR) recognition modes exist for gliadin epitopes remains unclear. TCR repertoire analysis revealed populations of HLA-DQ8-glia-α1 and HLA-DQ8.5-glia-γ1 restricted TRAV20(+)-TRBV9(+) T cells that did not possess a non-germline-encoded arginine residue...
October 4, 2016: Structure
Jilei Ma, Maopeng Tian, Xionglin Fan, Qi Yu, Yukai Jing, Weihua Wang, Li Li, Zijie Zhou
There is an urgent need for a vaccine against tuberculosis (TB) that is more effective than the current sole licensed option. However, target antigens of Mycobacterium tuberculosis with the vaccine potential remain elusive. Five immunodominant antigens with characteristic expressions at the stages of primary infection (Ag85A), the regulation of nutrition and metabolism when transferring from rapid growth to latency (PhoY2 and Rv3407), latency (Rv2626c), and reactivation (RpfB) were selected to construct the fusion polyprotein WH121, which has better immunogenicity and protection than each multistage antigen...
August 23, 2016: Oncotarget
Courtney S Malo, Danielle N Renner, April M Huseby Kelcher, Fang Jin, Michael J Hansen, Kevin D Pavelko, Aaron J Johnson
Virus vector-based vaccination against tumor-specific antigens remains a promising therapeutic approach to overcome the immune suppressive tumor microenvironment. However, the extent that the desired CD8 T cell response against the targeted tumor antigen is impacted by the CD8 T cell response against the virus vector is unclear. To address this question, we used picornavirus vaccination with Theiler's murine encephalomyelitis virus (TMEV) as our vector against tumor-expressed ovalbumin (OVA257-264) antigen in both the B16-OVA murine melanoma and GL261-quad cassette murine glioma models...
2016: PloS One
Sandra Rosskopf, Sabrina Jutz, Alina Neunkirchner, Martín R Candia, Beatrice Jahn-Schmid, Barbara Bohle, Winfried F Pickl, Peter Steinberger
We have generated engineered APC to present immunodominant peptides derived from the major aero-allergens of birch and mugwort pollen, Bet v 1142-153 and Art v 125-36, respectively. Jurkat-based T cell reporter lines expressing the cognate allergen-specific T cell receptors were used to read out the presentation of allergenic peptides on the engineered APC. Different modalities of peptide loading and presentation on MHC class II molecules were compared. Upon exogenous loading with allergenic peptides, the engineered APC elicited a dose-dependent response in the reporter T cells and the presence of chemical loading enhancers strongly increased reporter activation...
2016: Scientific Reports
Juliane Klehmet, Sarah Hoffmann, Gerrit Walter, Christian Meisel, Andreas Meisel
Whether and when auto-reactivity after stroke occurs is still a matter of debate. By using overlapping 15mer peptide pools consisting of myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) we show increased frequencies of immunodominant MOG- and MBP T cell responses in acute ischemic stroke which were associated with reduced frequencies of naïve T cells as well as CD8+ TEMRA cells. Auto-reactive CNS antigen-specific T cells responses as well as alterations of T cell subpopulations normalized in long-term follow up after stroke...
September 15, 2016: Journal of the Neurological Sciences
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