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Immunodominant T cell

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https://www.readbyqxmd.com/read/29661928/identification-and-evaluation-of-novel-protective-antigens-for-the-development-of-a-candidate-tb-subunit-vaccine
#1
Elena Stylianou, Rachel Harrington-Kandt, Julia Beglov, Naomi Bull, Nawamin Pinpathomrat, Gwendolyn M Swarbrick, Deborah A Lewinsohn, David M Lewinsohn, Helen McShane
The development of a vaccine against tuberculosis (TB), a disease caused by Mycobacterium tuberculosis ( M.tb ), is urgently needed. The only currently available vaccine, BCG, has variable efficacy. One approach in the global vaccine development effort is focused on boosting BCG using subunit vaccines. The identification of novel antigens for inclusion in subunit vaccines is a critical step in the TB vaccine development pathway. We selected four novel mycobacterial antigens recognised during the course of human infection...
April 16, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29650949/treating-cat-allergy-with-monoclonal-igg-antibodies-that-bind-allergen-and-prevent-ige-engagement
#2
J M Orengo, A R Radin, V Kamat, A Badithe, L H Ben, B L Bennett, S Zhong, D Birchard, A Limnander, A Rafique, J Bautista, A Kostic, D Newell, X Duan, M C Franklin, W Olson, T Huang, N A Gandhi, L Lipsich, N Stahl, N J Papadopoulos, A J Murphy, G D Yancopoulos
Acute allergic symptoms are caused by allergen-induced crosslinking of allergen-specific immunoglobulin E (IgE) bound to Fc-epsilon receptors on effector cells. Desensitization with allergen-specific immunotherapy (SIT) has been used for over a century, but the dominant protective mechanism remains unclear. One consistent observation is increased allergen-specific IgG, thought to competitively block allergen binding to IgE. Here we show that the blocking potency of the IgG response to Cat-SIT is heterogeneous...
April 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29648490/therapeutic-conserved-elements-ce-dna-vaccine-induces-strong-t-cell-responses-against-highly-conserved-viral-sequences-during-simian-human-immunodeficiency-virus-infection
#3
Paul Munson, Yi Liu, Debra Bratt, James T Fuller, Xintao Hu, George N Pavlakis, Barbara K Felber, James I Mullins, Deborah Heydenburg Fuller
HIV-specific T-cell responses play a key role in controlling HIV infection, and therapeutic vaccines for HIV that aim to improve viral control will likely need to improve on the T-cell responses induced by infection. However, in the setting of chronic infection, an effective therapeutic vaccine must overcome the enormous viral genetic diversity and the presence of pre-existing T-cell responses that are biased toward immunodominant T-cell epitopes that can readily mutate to evade host immunity and thus potentially provide inferior protection...
April 12, 2018: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/29620508/increasing-antigen-presentation-on-hsv-1-infected-cells-increases-lesion-size-but-does-not-alter-neural-infection-or-latency
#4
Tiffany A Russell, Thilaga Velusamy, Yeu-Yang Tseng, David C Tscharke
CD8+ T cells have a role in the control of acute herpes simplex virus (HSV) infection and may also be important in the maintenance of latency. In this study we have explored the consequences of boosting the efficacy of CD8+ T cells against HSV by increasing the amount of an MHC I-presented epitope on the surface of infected cells. To do this we used HSVs engineered to express an extra copy of the immunodominant CD8+ T cell epitope in C57Bl/6 mice, namely gB498 (SSIEFARL). Despite greater presentation of gB498 on infected cells, CD8+ T cell responses to these viruses in mice were similar to those elicited by a control virus...
April 5, 2018: Journal of General Virology
https://www.readbyqxmd.com/read/29599759/emergence-of-cd4-and-cd8-polyfunctional-t-cell-responses-against-immunodominant-lytic-and-latent-ebv-antigens-in-children-with-primary-ebv-infection
#5
Janice K P Lam, K F Hui, Raymond J Ning, X Q Xu, K H Chan, Alan K S Chiang
Long term carriers were shown to generate robust polyfunctional T cell (PFC) responses against lytic and latent antigens of Epstein-Barr virus (EBV). However, the time of emergence of PFC responses against EBV antigens, pattern of immunodominance and difference between CD4+ and CD8+ T cell responses during various stages of EBV infection are not clearly understood. A longitudinal study was performed to assess the development of antigen-specific PFC responses in children diagnosed to have primary symptomatic (infectious mononucleosis [IM]) and asymptomatic (AS) EBV infection...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29588155/identification-of-immunodominant-th2-cell-epitopes-in-chinese-bullous-pemphigoid-patients
#6
Jieyu Zhang, Hui Fang, Shengxian Shen, Erle Dang, Qiuju Li, Pei Qiao, Hongjiang Qiao, Gang Wang
Bullous pemphigoid (BP) is a subepidermal autoimmune blistering disease caused by autoantibodies (autoAbs) targeting the juxtamembranous extracellular noncollagenous 16A (NC16A) domain of human collagen XVII (also known as BP180). Because T helper cells are essential for antibody responses to antigens, we adopted an assay to map the immunodominant Th2-cell epitopes in NC16A. We synthesized 22 overlapping peptides spanning the entire sequence of BP180-NC16A and investigated the reactivity of Th2 cells from BP patients to these peptides using the ELISPOT assay...
March 24, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29578071/the-phagosome-and-redox-control-of-antigen-processing
#7
REVIEW
Benjamin W Ewanchuk, Robin M Yates
In addition to debris clearance and antimicrobial function, versatile organelles known as phagosomes play an essential role in the processing of exogenous antigen in antigen presenting cells. While there has been much attention on human leukocyte antigen haplotypes in the determination of antigenic peptide repertoires, the lumenal biochemistries within phagosomes and endosomes are emerging as equally-important determinants of peptide epitope composition and immunodominance. Recently, the lumenal redox microenvironment within these degradative compartments has been shown to impact two key antigenic processing chemistries: proteolysis by lysosomal cysteine proteases and disulfide reduction of protein antigens...
March 22, 2018: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29556319/identification-of-an-hla-a2-restricted-cd147-epitope-that-can-induce-specific-ctl-cytotoxicity-against-drug-resistant-mcf-7-adr-cells
#8
Chuang Qu, Shuhui Gao, Hongwei Shao, Wenfeng Zhang, Huabben Bo, Xin Lu, Tianjiao Chen, Jing Kou, Yue Wang, Gui Si Chen, Shulin Huang, Han Shen
Cluster of differentiation (CD)147 is highly expressed in drug-resistant tumor cell lines and is involved in the formation of tumor drug resistance. Therefore, immunotherapy utilizing CD147 epitope peptides is a promising approach for the elimination of drug-resistant tumor cells. However, like most tumor-associated antigens (TAAs), CD147 belongs to the autoantigen category, and T cells that recognize high affinity, immunodominant epitopes from autoantigens are deleted though thymic negative selection. Furthermore, wild-type autoantigen peptides cannot effectively activate and expand T lymphocytes with lower affinity T cell receptors in vivo ...
April 2018: Oncology Letters
https://www.readbyqxmd.com/read/29552292/immunodominant-antigens-that-induce-th1-and-th17-responses-protect-mice-against-helicobacter-pylori-infection
#9
Heqiang Sun, Hanmei Yuan, Ranjing Tan, Bin Li, Gang Guo, Jinyong Zhang, Haiming Jing, Yi Qin, Zhuo Zhao, Quanming Zou, Chao Wu
Helicobacter pylori has infected more than half of the world's population, causing gastritis, gastric ulcers, gastric mucosa-associated lymphoid tissue lymphoma and gastric cancer. The oral recombinant Helicobacter pylori vaccine currently used has made great progress in addressing this problem, however, its efficacy and longevity still need to be improved. Th1 and Th17 cells play essential roles in local protection against Helicobacter pylori in the stomach mucosa. Additionally, protective immunodominant antigens are the preferred for a vaccine...
February 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29514902/dynamics-of-tissue-specific-cd8-t-cell-responses-during-west-nile-virus-infection
#10
Renan Aguilar-Valenzuela, Jason Netland, Young-Jin Seo, Michael J Bevan, Arash Grakoui, Mehul S Suthar
The mouse model of West Nile virus, which is a leading cause of mosquito-borne encephalitis worldwide, has provided fundamental insights into the host and viral factors that regulate viral pathogenesis and infection outcome. In particular, CD8+ T cells are critical for controlling WNV replication and promoting protection against infection. Here, we present the characterization of a T cell receptor (TCR) transgenic mouse with specificity to the immunodominant epitope in the WNV NS4B protein (herein referred to as transgenic WNV-I mice)...
March 7, 2018: Journal of Virology
https://www.readbyqxmd.com/read/29511082/igg-responses-to-porins-and-lipopolysaccharide-within-an-outer-membrane-based-vaccine-against-nontyphoidal-salmonella-develop-at-discordant-rates
#11
Anna E Schager, C Coral Dominguez-Medina, Francesca Necchi, Francesca Micoli, Yun Shan Goh, Margaret Goodall, Adriana Flores-Langarica, Saeeda Bobat, Charlotte N L Cook, Melissa Arcuri, Arianna Marini, Lloyd D W King, Faye C Morris, Graham Anderson, Kai-Michael Toellner, Ian R Henderson, Constantino López-Macías, Calman A MacLennan, Adam F Cunningham
Antibodies acquired after vaccination or natural infection with Gram-negative bacteria, such as invasive Salmonella enterica serovar Typhimurium, can protect against disease. Immunization with naturally shed outer membrane vesicles from Gram-negative bacteria is being studied for its potential to protect against many infections, since antigens within vesicles maintain their natural conformation and orientation. Shedding can be enhanced through genetic modification, and the resulting particles, generalized modules for membrane antigens (GMMA), not only offer potential as vaccines but also can facilitate the study of B-cell responses to bacterial antigens...
March 6, 2018: MBio
https://www.readbyqxmd.com/read/29509778/immunodominance-in-t-cell-responses-elicited-against-different-domains-of-detoxified-pneumolysin-plyd1
#12
Els van Westen, Martien C M Poelen, Germie P J M van den Dobbelsteen, Eliud O Oloo, Martina M Ochs, Nynke Y Rots, Cecile A C M van Els
Detoxified pneumolysin, PlyD1, is a protein vaccine candidate that induces protection against infections with Streptococcus pneumoniae in mouse models. Despite extensive knowledge on antibody responses against PlyD1, limited information is available about PlyD1 induced T cell recognition. Here we interrogated epitope breadth and functional characteristics of the T cell response to PlyD1 in two mouse strains. BALB/c (H-2d) and C57BL/6 (H-2b) mice were vaccinated with Al(OH)3-adjuvanted or non-adjuvanted PlyD1, or placebo, on day 0, 21 and 42 and were sacrificed at day 56 for collection of sera and spleens...
2018: PloS One
https://www.readbyqxmd.com/read/29503651/antigen-loading-e-g-glutamic-acid-decarboxylase-65-of-tolerogenic-dcs-toldcs-reduces-their-capacity-to-prevent-diabetes-in-the-non-obese-diabetes-nod-severe-combined-immunodeficiency-model-of-adoptive-cotransfer-of-diabetes-as-well-as-in-nod-mice
#13
David P Funda, Jaroslav Goliáš, Tomáš Hudcovic, Hana Kozáková, Radek Špíšek, Lenka Palová-Jelínková
Tolerogenic DCs (tolDCs) are being researched as a promising intervention strategy also in autoimmune diseases including type 1 diabetes (T1D). T1D is a T-cell-mediated, organ-specific disease with several well-defined and rather specific autoantigens, i.e., proinsulin, insulin, glutamic acid decarboxylase 65 (GAD65), that have been used in animal as well as human intervention trials in attempts to achieve a more efficient, specific immunotherapy. In this study, we have tested tolerogenic DCs for their effectiveness to prevent adoptive transfer of diabetes by diabetogenic splenocytes into non-obese diabetes (NOD)-severe combined immunodeficiency (NOD-SCID) recipients...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29487600/allergen-and-epitope-targets-of-mouse-specific-t-cell-responses-in-allergy-and-asthma
#14
Véronique Schulten, Luise Westernberg, Giovanni Birrueta, John Sidney, Sinu Paul, Paula Busse, Bjoern Peters, Alessandro Sette
Mouse allergy has become increasingly common, mainly affecting laboratory workers and inner-city households. To date, only one major allergen, namely Mus m 1, has been described. We sought to identify T cell targets in mouse allergic patients. PBMC from allergic donors were expanded with either murine urine or epithelial extract and subsequently screened for cytokine production (IL-5 and IFNγ) in response to overlapping peptides spanning the entire Mus m 1 sequence, peptides from various Mus m 1 isoforms [major urinary proteins (MUPs)], peptides from mouse orthologs of known allergens from other mammalian species and peptides from proteins identified by immunoproteomic analysis of IgE/IgG immunoblots of mouse urine and epithelial extracts...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29466365/cross-reactive-microbial-peptides-can-modulate-hiv-specific-cd8-t-cell-responses
#15
Christopher W Pohlmeyer, Sarah B Laskey, Sarah E Beck, Daniel C Xu, Adam A Capoferri, Caroline C Garliss, Megan E May, Alison Livingston, Walt Lichmira, Richard D Moore, M Sue Leffell, Nicholas J Butler, Jennifer E Thorne, John A Flynn, Robert F Siliciano, Joel N Blankson
Heterologous immunity is an important aspect of the adaptive immune response. We hypothesized that this process could modulate the HIV-1-specific CD8+ T cell response, which has been shown to play an important role in HIV-1 immunity and control. We found that stimulation of peripheral blood mononuclear cells (PBMCs) from HIV-1-positive subjects with microbial peptides that were cross-reactive with immunodominant HIV-1 epitopes resulted in dramatic expansion of HIV-1-specific CD8+ T cells. Interestingly, the TCR repertoire of HIV-1-specific CD8+ T cells generated by ex vivo stimulation of PBMCs using HIV-1 peptide was different from that of cells stimulated with cross-reactive microbial peptides in some HIV-1-positive subjects...
2018: PloS One
https://www.readbyqxmd.com/read/29456015/multi-antigenic-human-cytomegalovirus-mrna-vaccines-that-elicit-potent-humoral-and-cell-mediated-immunity
#16
Shinu John, Olga Yuzhakov, Angela Woods, Jessica Deterling, Kimberly Hassett, Christine A Shaw, Giuseppe Ciaramella
A cytomegalovirus (CMV) vaccine that is effective at preventing congenital infection and reducing CMV disease in transplant patients remains a high priority as no approved vaccines exist. While the precise correlates of protection are unknown, neutralizing antibodies and antigen-specific T cells have been implicated in controlling infection. We demonstrate that the immunization of mice and nonhuman primates (NHPs) with lipid nanoparticles (LNP) encapsulating modified mRNA encoding CMV glycoproteins gB and pentameric complex (PC) elicit potent and durable neutralizing antibody titers...
March 14, 2018: Vaccine
https://www.readbyqxmd.com/read/29444872/fviii-proteins-with-a-modified-immunodominant-t-cell-epitope-exhibit-reduced-immunogenicity-and-normal-fviii-activity
#17
Ruth A Ettinger, Joseph A Liberman, Devi Gunasekera, Komal Puranik, Eddie A James, Arthur R Thompson, Kathleen P Pratt
Factor VIII (FVIII)-neutralizing antibodies (inhibitors) are a serious complication in hemophilia A (HA). The peptide FVIII 2194-2213 contains an immunodominant HLA-DRA*01-DRB1*01:01 (DRB1*01:01)-restricted epitope recognized by CD4 + T-effector cells from HA subjects. The aim of this study was to identify amino acid substitutions to deimmunize this epitope while retaining procoagulant function and expression levels comparable to those of wild-type (WT) FVIII proteins. The shortest DRB1*01:01-binding peptide was FVIII 2194-2205 , and residues important for affinity were identified as F2196, M2199, A2201, and S2204...
February 27, 2018: Blood Advances
https://www.readbyqxmd.com/read/29444189/cross-priming-induces-immunodomination-in-the-presence-of-viral-mhc-class-i-inhibition
#18
Elvin J Lauron, Liping Yang, Jabari I Elliott, Maria D Gainey, Daved H Fremont, Wayne M Yokoyama
Viruses have evolved mechanisms of MHCI inhibition in order to evade recognition by cytotoxic CD8+ T cells (CTLs), which is well-illustrated by our prior studies on cowpox virus (CPXV) that encodes potent MHCI inhibitors. Deletion of CPXV viral MHCI inhibitors markedly attenuated in vivo infection due to effects on CTL effector function, not priming. However, the CTL response to CPXV in C57BL/6 mice is dominated by a single peptide antigen presented by H-2Kb. Here we evaluated the effect of viral MHCI inhibition on immunodominant (IDE) and subdominant epitopes (SDE) as this has not been thoroughly examined...
February 2018: PLoS Pathogens
https://www.readbyqxmd.com/read/29443102/expression-of-exogenous-antigens-in-the-mycobacterium-bovis-bcg-vaccine-via-non-genetic-surface-decoration-with-the-avidin-biotin-system
#19
Ting-Yu Angela Liao, Alice Lau, Joseph Sunil, Vesa Hytönen, Zakaria Hmama
Tuberculosis (TB) is a serious infectious disease and the only available vaccine M. bovis bacillus Calmette-Guérin (BCG) is safe and effective for protection against children's severe TB meningitis and some forms of disseminated TB, but fails to protect against pulmonary TB, which is the most prevalent form of the disease. Promising strategies to improve BCG currently rely either on its transformation with genes encoding immunodominant M. tuberculosis (Mtb)-specific antigens and/or complementation with genes encoding co-factors that would stimulate antigen presenting cells...
January 31, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29437954/t-cell-receptors-for-the-hiv-kk10-epitope-from-patients-with-differential-immunologic-control-are-functionally-indistinguishable
#20
Alok V Joglekar, Zhe Liu, Jeffrey K Weber, Yong Ouyang, John D Jeppson, Won Jun Noh, Pedro A Lamothe-Molina, Huabiao Chen, Seung-Gu Kang, Michael T Bethune, Ruhong Zhou, Bruce D Walker, David Baltimore
HIV controllers (HCs) are individuals who can naturally control HIV infection, partially due to potent HIV-specific CD8+ T cell responses. Here, we examined the hypothesis that superior function of CD8+ T cells from HCs is encoded by their T cell receptors (TCRs). We compared the functional properties of immunodominant HIV-specific TCRs obtained from HLA-B*2705 HCs and chronic progressors (CPs) following expression in primary T cells. T cells transduced with TCRs from HCs and CPs showed equivalent induction of epitope-specific cytotoxicity, cytokine secretion, and antigen-binding properties...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
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