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Immunodominant T cell

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https://www.readbyqxmd.com/read/29466365/cross-reactive-microbial-peptides-can-modulate-hiv-specific-cd8-t-cell-responses
#1
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
#2
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...
February 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
#3
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
#4
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
#5
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
#6
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 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29435138/personalized-adoptive-immunotherapy-for-patients-with-ebv-associated-tumors-and-complications-evaluation-of-novel-naturally-processed-and-presented-ebv-derived-t-cell-epitopes
#7
Maren Bieling, Sabine Tischer, Ulrich Kalinke, Rainer Blasczyk, Søren Buus, Britta Maecker-Kolhoff, Britta Eiz-Vesper
Morbidity and mortality of immunocompromised patients are increased by primary infection with or reactivation of Epstein-Barr virus (EBV), possibly triggering EBV+ post-transplant lymphoproliferative disease (PTLD). Adoptive transfer of EBV-specific cytotoxic T cells (EBV-CTLs) promises a non-toxic immunotherapy to effectively prevent or treat these complications. To improve immunotherapy and immunomonitoring this study aimed at identifying and evaluating naturally processed and presented HLA-A*03:01-restricted EBV-CTL epitopes as immunodominant targets...
January 12, 2018: Oncotarget
https://www.readbyqxmd.com/read/29419434/deep-sequencing-and-flow-cytometric-characterization-of-expanded-effector-memory-cd8-cd57-t-cells-frequently-reveals-t-cell-receptor-v%C3%AE-oligoclonality-and-cdr3-homology-in-acquired-aplastic-anemia
#8
Valentina Giudice, Xingmin Feng, Zenghua Lin, Wei Hu, Fanmao Zhang, Wangmin Qiao, Maria Del Pilar Fernandez Ibanez, Olga Rios, Neal S Young
Oligoclonal expansion of CD8+CD28- lymphocytes has been considered indirect evidence for a pathogenic immune response in acquired aplastic anemia. A subset of CD8+CD28- cells with CD57 expression termed effector memory cells is expanded in several immune mediated diseases and may have a role in immune surveillance. We hypothesized that effector memory CD8+CD28-CD57+ cells may drive aberrant oligoclonal expansion in aplastic anemia. We found CD8+CD57+ cells frequently expanded in the blood of aplastic anemia patients, with oligoclonal characteristics by flow cytometric Vβ usage analysis: skewing in 1 to 5 Vβ families and frequencies of immunodominant clones ranging from 1...
February 1, 2018: Haematologica
https://www.readbyqxmd.com/read/29391203/analysis-of-genetic-diversity-and-population-structure-of-gene-encoding-cell-traversal-protein-for-ookinetes-and-sporozoites-celtos-vaccine-candidate-antigen-in-global-plasmodium-falciparum-populations
#9
Sakineh Pirahmadi, Sedigheh Zakeri, Akram Abouie Mehrizi, Navid Dinparast Djadid
Plasmodium falciparum cell-traversal protein for ookinetes and sporozoites (PfCelTOS) has been reported as one of the most attractive malaria vaccine candidate antigens. To design a broadly effective malaria vaccine based on this antigen, it is crucial to have adequate information on genetic diversity in global PfCelTOS. Therefore, the extent of sequence diversity at the full-length of the pfceltos was assessed among both natural P. falciparum isolates collected from Iran (n = 93) and from available global pfceltos sequence data retrieved from PlasmoDB database (n = 159)...
January 29, 2018: Infection, Genetics and Evolution
https://www.readbyqxmd.com/read/29382733/virulence-role-of-the-glcnac-side-chain-of-the-lancefield-cell-wall-carbohydrate-antigen-in-non-m1-serotype-group-a-streptococcus
#10
Anna Henningham, Mark R Davies, Satoshi Uchiyama, Nina M van Sorge, Sean Lund, Kelsey T Chen, Mark J Walker, Jason N Cole, Victor Nizet
Classification of streptococci is based upon expression of unique cell wall carbohydrate antigens. All serotypes of group A Streptococcus (GAS; Streptococcus pyogenes), a leading cause of infection-related mortality worldwide, express the group A carbohydrate (GAC). GAC, the classical Lancefield antigen, is comprised of a polyrhamnose backbone with N-acetylglucosamine (GlcNAc) side chains. The immunodominant GlcNAc epitope of GAC is the basis of all rapid diagnostic testing for GAS infection. We previously identified the 12-gene GAC biosynthesis gene cluster and determined that the glycosyltransferase GacI was required for addition of the GlcNAc side chain to the polyrhamnose core...
January 30, 2018: MBio
https://www.readbyqxmd.com/read/29374075/effects-of-cross-presentation-antigen-processing-and-peptide-binding-in-hiv-evasion-of-t-cell-immunity
#11
Blake F Frey, Jiansheng Jiang, Yongjun Sui, Lisa F Boyd, Bin Yu, Gwen Tatsuno, Rolf Billeskov, Shahram Solaymani-Mohammadi, Phillip W Berman, David H Margulies, Jay A Berzofsky
Unlike cytosolic processing and presentation of viral Ags by virus-infected cells, Ags first expressed in infected nonprofessional APCs, such as CD4+ T cells in the case of HIV, are taken up by dendritic cells and cross-presented. This generally requires entry through the endocytic pathway, where endosomal proteases have first access for processing. Thus, understanding virus escape during cross-presentation requires an understanding of resistance to endosomal proteases, such as cathepsin S (CatS). We have modified HIV-1MN gp120 by mutating a key CatS cleavage site (Thr322Thr323) in the V3 loop of the immunodominant epitope IGPGRAFYTT to IGPGRAFYVV to prevent digestion...
January 26, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29371615/retinoic-acid-prevents-immunogenicity-of-milk-lipocalin-bos-d-5-through-binding-to-its-immunodominant-t-cell-epitope
#12
Karin Hufnagl, Debajyoti Ghosh, Stefanie Wagner, Alessandro Fiocchi, Lamia Dahdah, Rodolfo Bianchini, Nina Braun, Ralf Steinborn, Martin Hofer, Marion Blaschitz, Georg A Roth, Gerlinde Hofstetter, Franziska Roth-Walter, Luis F Pacios, Erika Jensen-Jarolim
The major cow's milk allergen Bos d 5 belongs to the lipocalin protein family, with an intramolecular pocket for hydrophobic ligands. We investigated whether Bos d 5 when loaded with the active vitamin A metabolite retinoic acid (RA), would elicit differential immune responses compared to the unloaded state. By in silico docking an affinity energy of -7.8 kcal/mol was calculated for RA into Bos d 5. Loading of RA to Bos d 5 could be achieved in vitro, as demonstrated by ANS displacement assay, but had no effect on serum IgE binding in tolerant or challenge-positive milk allergic children...
January 25, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29362503/alloantigen-expression-on-malignant-cells-and-healthy-host-tissue-influences-graft-versus-tumor-reactions-after-allogeneic-hematopoietic-stem-cell-transplantation
#13
Stella Robert, Jörn C Albring, Karin Frebel, Corinna Opitz, Jennifer Urh, Claudia Wolf, Christine Heinrich, Wolfgang E Berdel, Matthias Stelljes
Durable remissions of hematological malignancies regularly observed following allogeneic hematopoietic stem cell transplantation (aHSCT) are due to the conditioning regimen, as well as an immunological phenomenon called graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) effect. The development of GVL is closely linked to graft-versus-host disease (GVHD), the main side effect associated with aHSCT. Both, GVHD and GVL are mediated by donor T cells that are initially activated by antigen-presenting cells that present recipient-derived alloantigens in the context of either matched or mismatched MHC class I molecules...
January 23, 2018: Bone Marrow Transplantation
https://www.readbyqxmd.com/read/29355985/identification-of-t-cell-epitopes-from-benzylpenicillin-conjugated-to-human-serum-albumin-and-implication-in-penicillin-allergy
#14
Marie Eliane Azoury, Lucia Filì, Rami Bechara, Noémie Scornet, Luc de Chaisemartin, Richard J Weaver, Nancy Claude, Bernard Maillere, Paola Parronchi, Delphine Joseph, Marc Pallardy
BACKGROUND: There is in vitro evidence that T-cells from allergic patients react to benzylpenicillin-human serum albumin (BP-HSA) bioconjugates. Our group has recently shown the existence of naïve CD4+ T lymphocytes recognizing BP-HSA in healthy donors. However, BP-haptenated peptides from HSA participating in the immunization of allergic patients have never been identified. The purpose of the present study is to identify immunodominant BP-haptenated peptides from HSA involved in immunization of patients to BP and to refine the frequency calculation of naïve CD4+ T-cells recognizing BP...
January 22, 2018: Allergy
https://www.readbyqxmd.com/read/29343295/cytotoxic-t-lymphocytes-from-cattle-sharing-the-same-mhc-class-i-haplotype-and-immunized-with-live-theileria-parva-sporozoites-differ-in-antigenic-specificity
#15
Lucilla Steinaa, Nicholas Svitek, Elias Awino, Rosemary Saya, Philip Toye
OBJECTIVES: The objective of this study was to assess whether cytotoxic T cells (CTL) generated by the live vaccine, known as "ITM Muguga cocktail", which is used for the cattle disease East Cost fever (ECF) in Sub-Saharan Africa, showed a broad reactivity against many different strains of the causative parasite Theileria parva. We also assessed whether immune responses were similar in cattle expressing the same MHC class I haplotypes. RESULTS: The antigenic specificity of CTL from MHC class I-matched cattle vaccinated with the Muguga cocktail were different...
January 17, 2018: BMC Research Notes
https://www.readbyqxmd.com/read/29330423/t-cell-immunity-to-zika-virus-targets-immunodominant-epitopes-that-show-cross-reactivity-with-other-flaviviruses
#16
C J Reynolds, O M Suleyman, A M Ortega-Prieto, J K Skelton, P Bonnesoeur, A Blohm, V Carregaro, J S Silva, E A James, B Maillère, M Dorner, R J Boyton, D M Altmann
Zika virus (ZIKV) Infection has several outcomes from asymptomatic exposure to rash, conjunctivitis, Guillain-Barré syndrome or congenital Zika syndrome. Analysis of ZIKV immunity is confounded by the fact that several related Flaviviruses infect humans, including Dengue virus 1-4, West Nile virus and Yellow Fever virus. HLA class II restricted T cell cross-reactivity between ZIKV and other Flaviviruses infection(s) or vaccination may contribute to protection or to enhanced immunopathology. We mapped immunodominant, HLA class II restricted, CD4 epitopes from ZIKV Envelope (Env), and Non-structural (NS) NS1, NS3 and NS5 antigens in HLA class II transgenic mice...
January 12, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29313220/pemphigus-a-comprehensive-review-on-pathogenesis-clinical-presentation-and-novel-therapeutic-approaches
#17
REVIEW
Robert Pollmann, Thomas Schmidt, Rüdiger Eming, Michael Hertl
Pemphigus is a group of rare, potentially devastating autoimmune diseases of the skin and mucous membranes with high morbidity and potentially lethal outcome. The major clinical variant, pemphigus vulgaris (PV) is caused by a loss of intercellular adhesion of epidermal keratinocytes which is induced by IgG autoantibodies against components of desmosomes. Specifically, IgG against the desmosomal adhesion proteins, desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1), preferentially target their ectodomains which are presumably critical for the transinteraction and signalling function of these adhesion molecules...
January 8, 2018: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29312617/t-cell-responses-to-kshv-infection-a-systematic-approach
#18
Romin Roshan, Nazzarena Labo, Matthew Trivett, Wendell Miley, Vickie Marshall, Lori Coren, Elena M Cornejo Castro, Hannah Perez, Benjamin Holdridge, Eliza Davis, Rodrigo Matus-Nicodemos, Victor I Ayala, Raymond Sowder, Kathleen M Wyvill, Karen Aleman, Christine Fennessey, Jeffrey Lifson, Mark N Polizzotto, Daniel Douek, Brandon Keele, Thomas S Uldrick, Robert Yarchoan, Claes Ohlen, David Ott, Denise Whitby
Prior studies of T-cell responses to KSHV have included relatively few participants and focused on relatively few KSHV antigens. To provide a more comprehensive analysis, we investigated T-cell responses to the whole KSHV proteome using IFN-γ ELISpot. Using ∼7,500 overlapping 15mer peptides we generated one to three peptide pools for each of the 82 KSHV ORFs. IFN-γ ELISpot analysis of PBMCs from 19 patients with a history of KSHV-associated disease and 24 healthy donors (11 KSHV seropositive) detected widely varied responses...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29311380/hitting-the-target-how-t-cells-detect-and-eliminate-tumors
#19
REVIEW
Anthony E Zamora, Jeremy Chase Crawford, Paul G Thomas
The successes of antitumor immuno-based therapies and the application of next-generation sequencing to mutation profiling have produced insights into the specific targets of antitumor T cells. Mutated proteins have tremendous potential as targets for interventions using autologous T cells or engineered cell therapies and may serve as important correlates of efficacy for immunoregulatory interventions including immune checkpoint blockade. As mutated self, tumors present an exceptional case for host immunity, which has primarily evolved in response to foreign pathogens...
January 15, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29261651/long-lived-cd8-t-cell-responses-following-crimean-congo-haemorrhagic-fever-virus-infection
#20
Dominique Goedhals, Janusz T Paweska, Felicity J Burt
Crimean-Congo haemorrhagic fever virus (CCHFV) is a member of the Orthonairovirus genus of the Nairoviridae family and is associated with haemorrhagic fever in humans. Although T lymphocyte responses are known to play a role in protection from and clearance of viral infections, specific T cell epitopes have yet to be identified for CCHFV following infection. A panel of overlapping peptides covering the CCHFV nucleoprotein and the structural glycoproteins, GN and GC, were screened by ELISpot assay to detect interferon gamma (IFN-γ) production in vitro by peripheral blood mononuclear cells from eleven survivors with previous laboratory confirmed CCHFV infection...
December 19, 2017: PLoS Neglected Tropical Diseases
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