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Immunodominant T cell

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https://www.readbyqxmd.com/read/28428886/vaccination-with-inhibin-%C3%AE-provides-effective-immunotherapy-against-testicular-stromal-cell-tumors
#1
Robert Aguilar, Justin M Johnson, Patrick Barrett, Vincent K Tuohy
BACKGROUND: Testicular cancer is the most common male neoplasm occurring in men between the ages of 20 and 34. Although germ-line testicular tumors respond favorably to current standard of care, testicular stromal cell (TSC) tumors derived from Sertoli cells or Leydig cells often fail to respond to chemotherapy or radiation therapy and have a 5-year overall survival significantly lower than the more common and more treatable germ line testicular tumors. METHODS: To improve outcomes for TSC cancer, we have developed a therapeutic vaccine targeting inhibin-α, a protein produced by normal Sertoli and Leydig cells of the testes and expressed in the majority of TSC tumors...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428201/dihydrolipoamide-dehydrogenase-lpd-rv0462-specific-t-cell-recall-responses-are-higher-in-healthy-household-contacts-of-tb-a-novel-immunodominant-antigen-from-m-tuberculosis
#2
Santhi Devasundaram, Alamelu Raja
The partial effectiveness against pulmonary tuberculosis (PTB), displayed by the existing tuberculosis (TB) vaccine, bacillus Calmette-Guérin (BCG), highlights the need for novel vaccines to replace or improve BCG. In TB immunology, antigen-specific cellular immune response is frequently considered indispensable. Latency-associated antigens are intriguing as targets for TB vaccine development. The mycobacterial protein, dihydrolipoamide dehydrogenase (Lpd; Rv0462), the third enzyme of the pyruvate dehydrogenase (PDH) complex, facilitates Mycobacterium tuberculosis to resist host reactive nitrogen intermediates...
April 20, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28423320/sequence-and-structural-analyses-reveal-distinct-and-highly-diverse-human-cd8-tcr-repertoires-to-immunodominant-viral-antigens
#3
Guobing Chen, Xinbo Yang, Annette Ko, Xiaoping Sun, Mingming Gao, Yongqing Zhang, Alvin Shi, Roy A Mariuzza, Nan-Ping Weng
A diverse T cell receptor (TCR) repertoire is essential for controlling viral infections. However, information about TCR repertoires to defined viral antigens is limited. We performed a comprehensive analysis of CD8(+) TCR repertoires for two dominant viral epitopes: pp65495-503 (NLV) of cytomegalovirus and M158-66 (GIL) of influenza A virus. The highly individualized repertoires (87-5,533 α or β clonotypes per subject) comprised thousands of unique TCRα and TCRβ sequences and dozens of distinct complementary determining region (CDR)3α and CDR3β motifs...
April 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28421076/broad-based-cd4-t-cell-responses-to-influenza-a-virus-in-a-healthy-individual-who-lacks-typical-immunodominance-hierarchy
#4
Li Chen, Anjaleena Anthony, Sara Oveissi, Miaojuan Huang, Damien Zanker, Kun Xiao, Chao Wu, Quanming Zou, Weisan Chen
Influenza A virus (IAV) infection is a significant cause of morbidity and mortality worldwide. CD4(+) T cell responses have been shown to be important for influenza protection in mouse models and in human volunteers. IAV antigen-specific CD4(+) T cell responses were found to focus on matrix 1 (M1) and nucleoprotein (NP) at the protein antigen level. At the epitope level, only several epitopes within M1 and NP were recognized by CD4(+) T cells. And the epitope-specific CD4(+) T cell responses showed a typical immunodominance hierarchy in most of the healthy individuals studied...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28410427/tcr-stimulation-strength-is-inversely-associated-with-establishment-of-functional-brain-resident-memory-cd8-t-cells-during-persistent-viral-infection
#5
Saumya Maru, Ge Jin, Todd D Schell, Aron E Lukacher
Establishing functional tissue-resident memory (TRM) cells at sites of infection is a newfound objective of T cell vaccine design. To directly assess the impact of antigen stimulation strength on memory CD8 T cell formation and function during a persistent viral infection, we created a library of mouse polyomavirus (MuPyV) variants with substitutions in a subdominant CD8 T cell epitope that exhibit a broad range of efficiency in stimulating TCR transgenic CD8 T cells. By altering a subdominant epitope in a nonstructural viral protein and monitoring memory differentiation of donor monoclonal CD8 T cells in immunocompetent mice, we circumvented potentially confounding changes in viral infection levels, virus-associated inflammation, size of the immunodominant virus-specific CD8 T cell response, and shifts in TCR affinity that may accompany temporal recruitment of endogenous polyclonal cells...
April 14, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28408606/landscape-of-immunogenic-tumor-antigens-in-successful-immunotherapy-of-virally-induced-epithelial-cancer
#6
Sanja Stevanović, Anna Pasetto, Sarah R Helman, Jared J Gartner, Todd D Prickett, Bryan Howie, Harlan S Robins, Paul F Robbins, Christopher A Klebanoff, Steven A Rosenberg, Christian S Hinrichs
Immunotherapy has clinical activity in certain virally associated cancers. However, the tumor antigens targeted in successful treatments remain poorly defined. We used a personalized immunogenomic approach to elucidate the global landscape of antitumor T cell responses in complete regression of human papillomavirus-associated metastatic cervical cancer after tumor-infiltrating adoptive T cell therapy. Remarkably, immunodominant T cell reactivities were directed against mutated neoantigens or a cancer germline antigen, rather than canonical viral antigens...
April 14, 2017: Science
https://www.readbyqxmd.com/read/28404997/novel-fitc-labeled-igy-antibody-fluorescence-imaging-toxoplasma-gondii-in-vitro
#7
Mehtap Sert, Rabia Cakir Koc, Yasemin Budama Kilinc
Toxoplasmosis is caused by T. gondii and can create serious health problems in humans and also worldwide economic harm. Because of the clinical and veterinary importance of toxoplasmosis, its timely and accurate diagnosis has a major impact on disease-fighting strategies. T. gondii surface antigen 1 (SAG1), an immunodominant-specific antigen, is often used as a diagnostic tool. Therefore, the aim of this study was the optimization of novel fluorescein isothiocyanate (FITC) labeling of the SAG1-specific IgY antibody to show the potential for immunofluorescence imaging of T...
April 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28367149/major-histocompatibility-complex-mhc-class-i-and-mhc-class-ii-proteins-conformational-plasticity-in-antigen-presentation
#8
REVIEW
Marek Wieczorek, Esam T Abualrous, Jana Sticht, Miguel Álvaro-Benito, Sebastian Stolzenberg, Frank Noé, Christian Freund
Antigen presentation by major histocompatibility complex (MHC) proteins is essential for adaptive immunity. Prior to presentation, peptides need to be generated from proteins that are either produced by the cell's own translational machinery or that are funneled into the endo-lysosomal vesicular system. The prolonged interaction between a T cell receptor and specific pMHC complexes, after an extensive search process in secondary lymphatic organs, eventually triggers T cells to proliferate and to mount a specific cellular immune response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28341111/generation-characterization-and-immunogenicity-of-a-novel-chimeric-recombinant-protein-based-on-plasmodium-vivax-ama-1-and-msp119
#9
Mariana Vilela Rocha, Kátia Sanches Françoso, Luciana Chagas Lima, Tarsila Mendes Camargo, Ricardo L D Machado, Fabio T M Costa, Laurent Rénia, Francois Nosten, Bruce Russell, Mauricio M Rodrigues, Irene S Soares
Plasmodium vivax is the most widely distributed malaria species and the most prevalent species of malaria in America and Asia. Vaccine development against P. vivax is considered a priority in the global program for the eradication of malaria. Earlier studies have characterized the Apical Membrane Antigen 1 (AMA-1) ectodomain and the C-terminal region (19kDa) of the Merozoite Surface Protein 1 (MSP-1) of P. vivax as immunodominant antigens. Based on this characterization, we designed a chimeric recombinant protein containing both merozoite immunodominant domains (PvAMA166-MSP119)...
March 21, 2017: Vaccine
https://www.readbyqxmd.com/read/28326672/bk-polyomavirus-specific-9mer-cd8-t-cell-responses-correlate-with-clearance-of-bk-viremia-in-kidney-transplant-recipients-first-report-from-the-swiss-transplant-cohort-study-stcs
#10
Céline Leboeuf, Sabrina Wilk, Rita Achermann, Isabelle Binet, Dela Golshayan, Karin Hadaya, Cedric Hirzel, Matthias Hoffmann, Uyen Huynh-Do, Michael T Koller, Oriol Manuel, Nicolas J Mueller, Thomas F Mueller, Stefan Schaub, Christian van Delden, Fabian H Weissbach, Hans H Hirsch
BK polyomavirus (BKPyV) causes premature kidney transplant (KT) failure in 1-15% of patients. Since antivirals are lacking, most programs screen for BKPyV-viremia and, if positive, reduce immunosuppression. To evaluate the relationship of viremia and BKPyV-specific immunity, we examined prospectively cryopreserved plasma and PBMCs at T0, T6, and T12 months post-transplant from 28 viremic KT patients and 68 non-viremic controls matched for the transplantation period. BKPyV-IgG seroprevalence was comparable between cases (89...
March 22, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/28315221/t-cell-proliferation-assay-determination-of-immunodominant-t-cell-epitopes-of-food-allergens
#11
Madhan Masilamani, Mariona Pascal, Hugh A Sampson
Characterization of allergen-specific T cells is critical to understand their contribution to disease pathogenesis. The identification of immunodominant T-cell epitopes is crucial for development of T-cell-based vaccines. Peptide-specific T-cell proliferation studies are usually performed in a library of short synthetic peptides (15mer or 20mer) with 3 or 5 offset spanning the entire length of the allergen. T-cell peptide epitopes lack the primary and tertiary structure of the native protein to cross-link IgE, but retain the ability to stimulate T cells...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28288094/identification-of-zika-virus-epitopes-reveals-immunodominant-and-protective-roles-for-dengue-virus-cross-reactive-cd8-t-cells
#12
Jinsheng Wen, William Weihao Tang, Nicholas Sheets, Julia Ellison, Alessandro Sette, Kenneth Kim, Sujan Shresta
CD8(+) T cells play an important role in controlling Flavivirus infection, including Zika virus (ZIKV). Here, we have identified 25 HLA-B*0702-restricted epitopes and 1 HLA-A*0101-restricted epitope using interferon (IFN)-γ enzyme-linked immunospot (ELISPOT) and intracellular cytokine staining (ICS) in ZIKV-infected IFN-α/β receptor-deficient HLA transgenic mice. The cross-reactivity of ZIKV epitopes to dengue virus (DENV) was tested using IFN-γ-ELISPOT and IFN-γ-ICS on CD8(+) T cells from DENV-infected mice, and five cross-reactive HLA-B*0702-binding peptides were identified by both assays...
March 13, 2017: Nature Microbiology
https://www.readbyqxmd.com/read/28275375/a-comparative-phase-i-study-of-combination-homologous-subtype-c-dna-mva-and-env-gp140-protein-adjuvant-hiv-vaccines-in-two-immunization-regimes
#13
Sarah Joseph, Killian Quinn, Aldona Greenwood, Alethea V Cope, Paul F McKay, Peter J Hayes, Jakub T Kopycinski, Jill Gilmour, Aleisha N Miller, Christof Geldmacher, Yuka Nadai, Mohamed I M Ahmed, David C Montefiori, Len Dally, George Bouliotis, David J M Lewis, Roger Tatoud, Ralf Wagner, Mariano Esteban, Robin J Shattock, Sheena McCormack, Jonathan Weber
There remains an urgent need for a prophylactic HIV vaccine. We compared combined MVA and adjuvanted gp140 to sequential MVA/gp140 after DNA priming. We expected Env-specific CD4+ T-cells after DNA and MVA priming, and Env-binding antibodies in 100% individuals after boosting with gp140 and that combined vaccines would not compromise safety and might augment immunogenicity. Forty volunteers were primed three times with DNA plasmids encoding (CN54) env and (ZM96) gag-pol-nef at 0, 4 and 8 weeks then boosted with MVA-C (CN54 env and gag-pol-nef) and glucopyranosyl lipid adjuvant-aqueous formulation (GLA-AF) adjuvanted CN54gp140...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28270111/an-optimized-ifn-%C3%AE-elispot-assay-for-the-sensitive-and-standardized-monitoring-of-cmv-protein-reactive-effector-cells-of-cell-mediated-immunity
#14
Sascha Barabas, Theresa Spindler, Richard Kiener, Charlotte Tonar, Tamara Lugner, Julia Batzilla, Hanna Bendfeldt, Anne Rascle, Benedikt Asbach, Ralf Wagner, Ludwig Deml
BACKGROUND: In healthy individuals, Cytomegalovirus (CMV) infection is efficiently controlled by CMV-specific cell-mediated immunity (CMI). Functional impairment of CMI in immunocompromized individuals however can lead to uncontrolled CMV replication and severe clinical complications. Close monitoring of CMV-specific CMI is therefore clinically relevant and might allow a reliable prognosis of CMV disease as well as assist personalized therapeutic decisions. METHODS: Objective of this work was the optimization and technical validation of an IFN-γ ELISpot assay for a standardized, sensitive and reliable quantification of CMV-reactive effector cells...
March 7, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28250417/broad-tcr-repertoire-and-diverse-structural-solutions-for-recognition-of-an-immunodominant-cd8-t-cell-epitope
#15
InYoung Song, Anna Gil, Rabinarayan Mishra, Dario Ghersi, Liisa K Selin, Lawrence J Stern
A keystone of antiviral immunity is CD8(+) T cell recognition of viral peptides bound to MHC-I proteins. The recognition modes of individual T cell receptors (TCRs) have been studied in some detail, but the role of TCR variation in providing a robust response to viral antigens is unclear. The influenza M1 epitope is an immunodominant target of CD8(+) T cells that help to control influenza in HLA-A2(+) individuals. Here we show that CD8(+) T cells use many distinct TCRs to recognize HLA-A2-M1, which enables the use of different structural solutions to the problem of specifically recognizing a relatively featureless peptide antigen...
April 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28228754/proofreading-of-peptide-mhc-complexes-through-dynamic-multivalent-interactions
#16
REVIEW
Christoph Thomas, Robert Tampé
The adaptive immune system is able to detect and destroy cells that are malignantly transformed or infected by intracellular pathogens. Specific immune responses against these cells are elicited by antigenic peptides that are presented on major histocompatibility complex class I (MHC I) molecules and recognized by cytotoxic T lymphocytes at the cell surface. Since these MHC I-presented peptides are generated in the cytosol by proteasomal protein degradation, they can be metaphorically described as a window providing immune cells with insights into the state of the cellular proteome...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28218747/mhc-i-peptides-get-out-of-the-groove-and-enable-a-novel-mechanism-of-hiv-1-escape
#17
Phillip Pymm, Patricia T Illing, Sri H Ramarathinam, Geraldine M O'Connor, Victoria A Hughes, Corinne Hitchen, David A Price, Bosco K Ho, Daniel W McVicar, Andrew G Brooks, Anthony W Purcell, Jamie Rossjohn, Julian P Vivian
Major histocompatibility complex class I (MHC-I) molecules play a crucial role in immunity by capturing peptides for presentation to T cells and natural killer (NK) cells. The peptide termini are tethered within the MHC-I antigen-binding groove, but it is unknown whether other presentation modes occur. Here we show that 20% of the HLA-B*57:01 peptide repertoire comprises N-terminally extended sets characterized by a common motif at position 1 (P1) to P2. Structures of HLA-B*57:01 presenting N-terminally extended peptides, including the immunodominant HIV-1 Gag epitope TW10 (TSTLQEQIGW), showed that the N terminus protrudes from the peptide-binding groove...
April 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28212503/lactobacillus-buchneri-s-layer-as-carrier-for-an-ara-h-2-derived-peptide-for-peanut-allergen-specific-immunotherapy
#18
Julia Anzengruber, Merima Bublin, Eva Bönisch, Bettina Janesch, Angelika Tscheppe, Matthias L Braun, Eva-Maria Varga, Christine Hafner, Heimo Breiteneder, Christina Schäffer
Peanut allergy is an IgE-mediated severe hypersensitivity disorder. The lack of a treatment of this potentially fatal allergy has led to intensive research on vaccine development. Here, we describe the design and initial characterization of a carrier-bound peptide derived from the most potent peanut allergen, Ara h 2, as a candidate vaccine. Based on the adjuvant capability of bacterial surface (S-) layers, a fusion protein of the S-layer protein SlpB from Lactobacillus buchneri CD034 and the Ara h 2-derived peptide AH3a42 was produced...
May 2017: Molecular Immunology
https://www.readbyqxmd.com/read/28194152/hsp65-producing-lactococcus-lactis-prevents-inflammatory-intestinal-disease-in-mice-by-il-10-and-tlr2-dependent-pathways
#19
Ana Cristina Gomes-Santos, Rafael Pires de Oliveira, Thaís Garcias Moreira, Archimedes Barbosa Castro-Junior, Bernardo Coelho Horta, Luísa Lemos, Leonardo Augusto de Almeida, Rafael Machado Rezende, Denise Carmona Cara, Sérgio Costa Oliveira, Vasco Ariston Carvalho Azevedo, Anderson Miyoshi, Ana Maria Caetano Faria
Heat shock proteins (Hsps) are highly expressed at all sites of inflammation. As they are ubiquitous and immunodominant antigens, these molecules represent good candidates for the therapeutic use of oral tolerance in autoimmune and chronic inflammatory diseases. Evidences from human and animal studies indicate that inflammatory bowel disease (IBD) results from uncontrolled inflammatory responses to intestinal microbiota. Hsps are immunodominant proteins expressed by several immune cells and by commensal bacteria...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28188174/brain-atrophy-in-picornavirus-infected-fvb-mice-is-dependent-on-the-h-2d-b-class-i-molecule
#20
April M Huseby Kelcher, Pascal A Atanga, Jeffrey D Gamez, Luz M Cumba Garcia, Stephanie J Teclaw, Kevin D Pavelko, Slobodan I Macura, Aaron J Johnson
Brain atrophy is a common feature of numerous neurologic diseases in which the role of neuroinflammation remains ill-defined. In this study, we evaluated the contribution of major histocompatibility complex class I molecules to brain atrophy in Theiler's murine encephalomyelitis virus (TMEV)-infected transgenic FVB mice that express the D(b) class I molecule. FVB/D(b) and wild-type FVB mice were evaluated for changes in neuroinflammation, virus clearance, neuropathology, and development of brain atrophy via T2-weighted MRI and subsequent 3-dimensional volumetric analysis...
February 10, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
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