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https://www.readbyqxmd.com/read/29216561/design-synthesis-and-evaluation-of-an-anthraquinone-derivative-conjugated-to-myelin-basic-protein-immunodominant-mbp85-99-epitope-towards-selective-immunosuppression
#1
Anthi Tapeinou, Efstathia Giannopoulou, Carmen Simal, Bjarke E Hansen, Haralabos Kalofonos, Vasso Apostolopoulos, Alexios Vlamis-Gardikas, Theodore Tselios
Anthraquinone type compounds, especially di-substituted amino alkylamino anthraquinones have been widely studied as immunosuppressants. The anthraquinone ring is part of mitoxandrone that has been used for the treatment of multiple sclerosis (MS) and several types of tumors. A desired approach for the treatment of MS would be the immunosuppression and elimination of specific T cells that are responsible for the induction of the disease. Herein, the development of a peptide compound bearing an anthraquinone derivative with the potential to specifically destroy the encephalitogenic T cells responsible for the onset of MS is described...
November 24, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29209312/dual-molecular-mechanisms-govern-escape-at-immunodominant-hla-a2-restricted-hiv-epitope
#2
David K Cole, Anna Fuller, Garry Dolton, Efthalia Zervoudi, Mateusz Legut, Kim Miles, Lori Blanchfield, Florian Madura, Christopher J Holland, Anna M Bulek, John S Bridgeman, John J Miles, Andrea J A Schauenburg, Konrad Beck, Brian D Evavold, Pierre J Rizkallah, Andrew K Sewell
Serial accumulation of mutations to fixation in the SLYNTVATL (SL9) immunodominant, HIV p17 Gag-derived, HLA A2-restricted cytotoxic T lymphocyte epitope produce the SLFNTIAVL triple mutant "ultimate" escape variant. These mutations in solvent-exposed residues are believed to interfere with TCR recognition, although confirmation has awaited structural verification. Here, we solved a TCR co-complex structure with SL9 and the triple escape mutant to determine the mechanism of immune escape in this eminent system...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29206240/influence-of-an-immunodominant-herpes-simplex-virus-type-1-cd8-t-cell-epitope-on-the-target-hierarchy-and-function-of-subdominant-cd8-t-cells
#3
Benjamin R Treat, Sarah M Bidula, Srividya Ramachandran, Anthony J St Leger, Robert L Hendricks, Paul R Kinchington
Herpes simplex virus type 1 (HSV-1) latency in sensory ganglia such as trigeminal ganglia (TG) is associated with a persistent immune infiltrate that includes effector memory CD8+ T cells that can influence HSV-1 reactivation. In C57BL/6 mice, HSV-1 induces a highly skewed CD8+ T cell repertoire, in which half of CD8+ T cells (gB-CD8s) recognize a single epitope on glycoprotein B (gB498-505), while the remainder (non-gB-CD8s) recognize, in varying proportions, 19 subdominant epitopes on 12 viral proteins. The gB-CD8s remain functional in TG throughout latency, while non-gB-CD8s exhibit varying degrees of functional compromise...
December 4, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/29176865/pre-clinical-antigenicity-studies-of-an-innovative-multivalent-vaccine-for-human-visceral-leishmaniasis
#4
Pedro Cecílio, Begoña Pérez-Cabezas, Laura Fernández, Javier Moreno, Eugenia Carrillo, José M Requena, Epifanio Fichera, Steven G Reed, Rhea N Coler, Shaden Kamhawi, Fabiano Oliveira, Jesus G Valenzuela, Luigi Gradoni, Reinhard Glueck, Gaurav Gupta, Anabela Cordeiro-da-Silva
The notion that previous infection by Leishmania spp. in endemic areas leads to robust anti-Leishmania immunity, supports vaccination as a potentially effective approach to prevent disease development. Nevertheless, to date there is no vaccine available for human leishmaniasis. We optimized and assessed in vivo the safety and immunogenicity of an innovative vaccine candidate against human visceral leishmaniasis (VL), consisting of Virus-Like Particles (VLP) loaded with three different recombinant proteins (LJL143 from Lutzomyia longipalpis saliva as the vector-derived (VD) component, and KMP11 and LeishF3+, as parasite-derived (PD) antigens) and adjuvanted with GLA-SE, a TLR4 agonist...
November 27, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29176828/t-cell-recognition-of-mycobacterium-tuberculosis-peptides-presented-by-hla-e-derived-from-infected-human-cells
#5
Curtis McMurtrey, Melanie J Harriff, Gwendolyn M Swarbrick, Amanda Duncan, Meghan Cansler, Megan Null, Wilfried Bardet, Kenneth W Jackson, Deborah A Lewinsohn, William Hildebrand, David M Lewinsohn
HLA-E is a non-conventional MHC Class I molecule that has been recently demonstrated to present pathogen-derived ligands, resulting in the TCR-dependent activation of αβ CD8+ T cells. The goal of this study was to characterize the ligandome displayed by HLA-E following infection with Mycobacterium tuberculosis (Mtb) using an in-depth mass spectrometry approach. Here we identified 28 Mtb ligands derived from 13 different source proteins, including the Esx family of proteins. When tested for activity with CD8+ T cells isolated from sixteen donors, nine of the ligands elicited an IFN-γ response from at least one donor, with fourteen of 16 donors responding to the Rv0634A19-29 peptide...
2017: PloS One
https://www.readbyqxmd.com/read/29171068/a-t-cell-diagnostic-test-for-cystic-echinococcosis-based-on-antigen-b-peptides
#6
L Petrone, V Vanini, M Amicosante, A Corpolongo, M A Gomez Morales, A Ludovisi, G Ippolito, E Pozio, A Teggi, D Goletti
Cystic echinococcosis (CE) immunodiagnosis is still imperfect. We recently set-up a whole-blood test based on the interleukin (IL)-4 response to the native Antigen B (AgB) of Echinococcus granulosus. However, AgB is encoded by a multigene family coding for five putative subunits. Therefore, the aims of this study were to analyse the IL-4 response to peptides spanning the immunodominant regions of the five AgB subunits and to evaluate the accuracy of this assay for CE diagnosis. Peptides corresponding to each subunit were combined into five pools...
December 2017: Parasite Immunology
https://www.readbyqxmd.com/read/29167337/differential-immunodominance-hierarchy-of-cd8-t-cell-responses-in-hla-b-27-05-and-b-27-02-mediated-control-of-hiv-1-infection
#7
Emily Adland, Matilda Hill, Nora Lavandier, Anna Csala, Anne Edwards, Fabian Chen, Marek Radkowski, Justyna D Kowalska, Dimitrios Paraskevis, Angelos Hatzakis, Humberto Valenzuela-Ponce, Katja Pfafferott, Ian Williams, Pierre Pellegrino, Persephone Borrow, Masahiko Mori, Jürgen Rockstroh, Julia G Prado, Beatriz Mothe, Judith Dalmau, Javier Martinez-Picado, Gareth Tudor-Williams, John Frater, Anette Stryhn, Soren Buus, Gustavo Reyes Teran, Simon Mallal, Mina John, Susan Buchbinder, Gregory Kirk, Jeffrey Martin, Nelson Michael, Jacques Fellay, Steve Deeks, Bruce Walker, Santiago Avila-Rios, David Cole, Christian Brander, Mary Carrington, Philip Goulder
The well-characterised association between HLA-B*27:05 and protection against HIV disease progression has been linked to immunodominant HLA-B*27:05-restricted CD8+ T-cell responses towards the conserved Gag 263-272 ('KK10') and Pol 901-909 'KY9' epitopes. We here studied the impact of the 3 amino acid differences between HLA-B*27:05 and the closely-related HLA-B*27:02 on the HIV-specific CD8+ T-cell response hierarchy and on immune control of HIV. Genetic epidemiological data indicate that both HLA-B*27:02 and HLA-B*27:05 associate with slower disease progression and lower viral loads...
November 22, 2017: Journal of Virology
https://www.readbyqxmd.com/read/29163514/an-unexpected-major-role-for-proteasome-catalyzed-peptide-splicing-in-generation-of-t-cell-epitopes-is-there-relevance-for-vaccine-development
#8
REVIEW
Anouk C M Platteel, Juliane Liepe, Willem van Eden, Michele Mishto, Alice J A M Sijts
Efficient and safe induction of CD8(+) T cell responses is a desired characteristic of vaccines against intracellular pathogens. To achieve this, a new generation of safe vaccines is being developed accommodating single, dominant antigens of pathogens of interest. In particular, the selection of such antigens is challenging, since due to HLA polymorphism the ligand specificities and immunodominance hierarchies of pathogen-specific CD8(+) T cell responses differ throughout the human population. A recently discovered mechanism of proteasome-mediated CD8(+) T cell epitope generation, i...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29141529/experimental-autoimmune-encephalomyelitis-eae-model-of-cynomolgus-macaques-induced-by-recombinant-human-mog1-125-rhmog1-125-protein-and-mog34-56-peptide
#9
Yunxiao Sun, Zhen Peng, Libiao Zhang, Huaqian Wang, Xiangyang He, Xingwen Peng, Qin Zhang, Hui Liu, Junhua Rao, Haifeng Wang, Jie Wu
Experimental autoimmune encephalomyelitis (EAE) induced by self-myelin antigen is a widely used multiple sclerosis (MS) model for preclinical studies of new therapeutics and potential pathogenesis. By comparison with rodent EAE models, EAE models in primates are more similar to MS. Some groups have developed EAE models in primates by using common marmoset (Callithrix jacchus). However, this model has some limitations. EAE in cynomolgus monkey (Macaque fasciculrais) could overcome these limitations. In this study, EAE was induced in cynomolgus monkey by immunizing with the recombinant human myelin oligodendrocyte glycoprotein extracellular domain (1-125) (rhMOG1-125) and a synthetic peptide, representing peptide 34-56 of human myelin oligodendrocyte glycoprotein (MOG34-56) in complete Freund's adjuvant (CFA) and in combination with intravenous injection of pertussis toxin, and subsequent booster immunizations with the same dose of antigen in incomplete Freund's adjuvant (IFA) until the animals developed clinically significant EAE (score≥2)...
November 9, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/29121407/strong-and-frequent-t-cell-responses-to-the-minor-allergen-phl-p-12-in-spanish-patients-ige-sensitized-to-profilins
#10
Gitte Lund, Stephanie Brand, Tania Ramos, Lucia Jimeno, Patrice Boissy, Francisco Vega, Maria Arina, Lars Harder Christensen, Ilka Hoof, Kåre Hvalsøe Meno, Domingo Barber, Carlos Blanco, Peter Adler Würtzen, Peter Sejer Andersen
BACKGROUND: Profilins are dominant pan-allergens known to cause cross-sensitization, leading to clinical symptoms such as the pollen food syndrome. This study aims to determine the T-cell response to Phl p 12 in profilin-sensitized patients, by measuring the prevalence, strength and cross-reactivity to clinically relevant profilins. METHODS: The release of Phl p allergens from pollen was determined by mass spectrometry and immunochemistry. T-cell responses, epitope mapping and cross-reactivity to profilins (Phl p 12, Ole e 2, Bet v 2, and Mal d 4) were measured in-vitro using PBMCs from 26 Spanish grass allergic donors IgE-sensitized to profilin...
November 9, 2017: Allergy
https://www.readbyqxmd.com/read/29112951/phenotype-and-specificity-of-t-cells-in-primary-human-cytomegalovirus-infection-during-pregnancy-il-7rpos-long-term-memory-phenotype-is-associated-with-protection-from-vertical-transmission
#11
Federico Mele, Chiara Fornara, David Jarrossay, Milena Furione, Alessia Arossa, Arsenio Spinillo, Antonio Lanzavecchia, Giuseppe Gerna, Federica Sallusto, Daniele Lilleri
Congenital human cytomegalovirus (HCMV) infection is the major cause of birth defects and a precise definition of the HCMV-specific T-cell response in primary infection may help define reliable correlates of immune protection during pregnancy. In this study, a high throughput method was used to define the frequency of CD4+ and CD8+ T cells specific for four HCMV proteins in the naïve compartment of seronegative subjects and the effector/memory compartments of subjects with primary/remote HCMV infection. The naïve repertoire displayed comparable frequencies of T cells that were reactive with HCMV structural (pp65, gB and the pentamer gHgLpUL128L) and non-structural (IE-1) proteins...
2017: PloS One
https://www.readbyqxmd.com/read/29090224/production-and-evaluation-of-specific-single-chain-antibodies-against-ctla-4-for-cancer-targeted-therapy
#12
Farideh Hosseinzadeh, Saeed Mohammadi, Foroogh Nejatollahi
BACKGROUND: Cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) molecules are expressed on T-cells and inhibit their function by inhibiting activation of subsequent T-cell molecular pathways. Blocking of CTLA-4 inhibits the growth of malignant tumor cells. Anti-CTLA-4 monoclonal antibodies activate the immune system against cancer. Due to several advantages of single-chain antibodies (scFvs) compared to monoclonal antibodies in cancer immunotherapy, specific anti-CTLA-4 scFvs (single-chain variable fragment) were selected in this study...
October 2017: Reports of Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29081779/global-assessment-of-dengue-virus-specific-cd4-t-cell-responses-in-dengue-endemic-areas
#13
Alba Grifoni, Michael A Angelo, Benjamin Lopez, Patrick H O'Rourke, John Sidney, Cristhiam Cerpas, Angel Balmaseda, Cassia G T Silveira, Alvino Maestri, Priscilla R Costa, Anna P Durbin, Sean A Diehl, Elizabeth Phillips, Simon Mallal, Aruna D De Silva, Godwin Nchinda, Celine Nkenfou, Matthew H Collins, Aravinda M de Silva, Mei Qiu Lim, Paul A Macary, Filippo Tatullo, Tom Solomon, Vijaya Satchidanandam, Anita Desai, Vasanthapram Ravi, Josefina Coloma, Lance Turtle, Laura Rivino, Esper G Kallas, Bjoern Peters, Eva Harris, Alessandro Sette, Daniela Weiskopf
BACKGROUND: Dengue is a major public health problem worldwide. Assessment of adaptive immunity is important to understanding immunopathology and to define correlates of protection against dengue virus (DENV). To enable global assessment of CD4(+) T cell responses, we mapped HLA-DRB1-restricted DENV-specific CD4(+) T cell epitopes in individuals previously exposed to DENV in the general population of the dengue-endemic region of Managua, Nicaragua. METHODS: HLA class II epitopes in the population of Managua were identified by an in vitro IFNγ ELISPOT assay...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29066027/interferon-beta-specific-t-cells-are-associated-with-the-development-of-neutralizing-antibodies-in-interferon-beta-treated-multiple-sclerosis-patients
#14
Sudhakar Reddy Kalluri, Verena Grummel, Zsuzsanna Hracsko, Viola Pongratz, Verena Pernpeintner, Christiane Gasperi, Dorothea Buck, Bernhard Hemmer
Beta-interferons are still among the most commonly used drugs to treat Multiple Sclerosis (MS). The use of beta-interferons is limited by the development of anti-drug antibodies (ADA), which may abrogate the treatment effect of the drug. Although the antibody response has been well studied, little is known about the T cell response to interferon-beta (IFN-β). We investigated T cell responses in four treatment naïve MS patients and twenty-three patients treated with IFN-β who had or had not developed ADA to IFN-β...
October 20, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/29050772/ctl-immunogenicity-of-rv3615c-antigen-and-diagnostic-performances-of-an-esat-6-cfp-10-rv3615c-antigen-cocktail-for-mycobacterium-tuberculosis-infection
#15
Shuguang Tan, Nan Lin, Mingxiang Huang, Qing Wang, Yunhong Tan, Bingxi Li, Ning Zhang, Tianling Guo, Yingbin Cui, Xinchao Chen, Dongping Wang, Jue Wang, Haixia Xiao, William J Liu, Jinghua Yan, Catherine W-H Zhang, Cui Hua Liu, Kanglin Wan, George F Gao
T cell immune responses have played pivotal roles in host immune protection against Mycobacterium tuberculosis (MTB) infection. MTB specific antigen, Rv3615c (EspC), was identified to be as immunodominant as the well-known ESAT-6 and CFP-10, and has brought promising expectations to more sensitive T-cell based diagnosis and vaccine development. However, limited knowledge about the immunogenicity and diagnostic values of this antigen has restricted its application in clinical practice. Herein, the Rv3615c antigen was identified as a robust CTL immunoantigen with broadly cross-human leucocyte antigen (HLA) allele recognized peptides which may contribute to the broad recognition of Rv3615c antigen among the population...
December 2017: Tuberculosis
https://www.readbyqxmd.com/read/29032899/th1-epitope-peptides-induce-protective-immunity-against-rickettsia-rickettsii-infection-in-c3h-hen-mice
#16
Wenping Gong, Xiaolu Xiong, Pengcheng Wang, Jun Jiao, Xiaomei Yang, Bohai Wen
Rickettsia rickettsii is the causative pathogen of Rocky Mountain spotted fever (RMSF). Adr2, YbgF and OmpB are protective antigens of R. rickettsii. In this study, 90 candidate peptides were selected from these antigens based on their high-affinity binding capacity for the MHC class II molecule H2 I-A or H2 I-E using bioinformatic methods. Six peptides were determined using ELISPOT assay to be immunodominant based on the IFN-γ recall responses of CD4(+) T cells from mice immunized with R. rickettsii. Six nucleotide sequences encoding the immunodominant peptides were linked in series and inserted into a plasmid for expression in Escherichia coli cells, resulting in a new, recombinant polypeptide termed GWP...
October 9, 2017: Vaccine
https://www.readbyqxmd.com/read/28993513/dna-vaccination-by-electroporation-amplifies-broadly-cross-restricted-public-tcr-clonotypes-shared-with-hiv-controllers
#17
Madhura Mukhopadhyay, Moran Galperin, Mandar Patgaonkar, Sandhya Vasan, David D Ho, Alexandre Nouël, Mathieu Claireaux, Daniela Benati, Olivier Lambotte, Yaoxing Huang, Lisa A Chakrabarti
Rare patients who spontaneously control HIV replication provide a useful model to inform HIV vaccine development. HIV controllers develop particularly efficient antiviral CD4(+) T cell responses mediated by shared high-affinity TCRs. To determine whether the candidate DNA vaccine ADVAX could induce similar responses, we analyzed Gag-specific primary CD4(+) T cells from healthy volunteers who received ADVAX DNA by electroporation. Vaccinated volunteers had an immunodominant response to the Gag293 epitope with a functional avidity intermediate between that of controllers and treated patients...
November 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28975614/t-cell-receptor-alpha-variable-12-2-bias-in-the-immunodominant-response-to-yellow-fever-virus
#18
Amandine Bovay, Vincent Zoete, Garry Dolton, Anna M Bulek, David K Cole, Pierre J Rizkallah, Anna Fuller, Konrad Beck, Olivier Michielin, Daniel E Speiser, Andrew K Sewell, Silvia A Fuertes Marraco
The repertoire of human αβ T cell receptors (TCRs) is generated via somatic recombination of germline gene segments. Despite this enormous variation, certain epitopes can be immunodominant, associated with high frequencies of antigen-specific T cells and/or exhibit bias towards a TCR gene segment. Here, we studied the TCR repertoire of the HLA-A*0201-restricted epitope LLWNGPMAV (hereafter, A2/LLW) from Yellow Fever virus, which generates an immunodominant CD8(+) T cell response to the highly effective YF-17D vaccine...
October 3, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28968792/control-of-hiv-1-by-an-hla-b-52-01-c-12-02-protective-haplotype
#19
Takayuki Chikata, Hayato Murakoshi, Madoka Koyanagi, Kazutaka Honda, Hiroyuki Gatanaga, Shinichi Oka, Masafumi Takiguchi
HLA-B*52:01-C*12:02, which is found in approximately 20 % of all Japanese, is well known to be associated with ulcerative colitis and Takayasu arteritis. This haplotype is also known to be a protective one in HIV-1-infective individuals. Recent studies showed that HLA-B*52:01-restricted HIV-1-specific T cells suppress HIV-1 and that HLA-C*12:02 together with KIR2DL2 play an important role in NK cell-mediated control of HIV-1. However, the role of HLA-C*12:02-restricted CTLs in suppression of HIV-1 replication remains unknown...
September 14, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28959348/in-silico-perspectives-on-the-prediction-of-the-plp-s-epitopes-involved-in-multiple-sclerosis
#20
Zahra Zamanzadeh, Mitra Ataei, Seyed Massood Nabavi, Ghasem Ahangari, Mehdi Sadeghi, Mohammad Hosein Sanati
BACKGROUND: Multiple sclerosis (MS) is the most common autoimmune disease of the central nervous system (CNS). The main cause of the MS is yet to be revealed, but the most probable theory is based on the molecular mimicry that concludes some infections in the activation of T cells against brain auto-antigens that initiate the disease cascade. OBJECTIVES: The Purpose of this research is the prediction of the auto-antigen potency of the myelin proteolipid protein (PLP) in multiple sclerosis...
March 2017: Iranian Journal of Biotechnology
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