keyword
MENU ▼
Read by QxMD icon Read
search

T cell affinity

keyword
https://www.readbyqxmd.com/read/29034433/development-of-humanized-scfv-antibody-fragment-s-that-targets-and-blocks-specific-hla-alleles-linked-to-myasthenia-gravis
#1
B Vijayalakshmi Ayyar, M Zouhair Atassi
Myasthenia gravis (MG) is an autoimmune disease caused by sensitization of the immune system to self-antigens. We have previously shown that targeting MG-susceptible alleles can significantly inhibit proliferation of disease-specific T cells. In this work, we humanized a murine monoclonal antibody (mAb) LG11, capable of blocking MG-associated DQ beta 1 (DQB1) allele and reformatted it into single-chain fragment variable (scFv). A fully functional humanized scFv was obtained by optimizing variable domain orientations and linker lengths, along with the optimization of expression conditions and codons to suit Escherichia coli expression machinery...
October 15, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/29033912/the-infectious-basis-of-acpa-positive-rheumatoid-arthritis
#2
REVIEW
Lazaros I Sakkas, Dimitrios Daoussis, Stamatis-Nick Liossis, Dimitrios P Bogdanos
Rheumatoid arthritis (RA) is associated with HLA-DRB1 shared epitope (HLA-DRB1SE) and anti-citrullinated protein autoantibodies (ACPAs). ACPAs precedes the onset of clinical and subclinical RA. There are strong data for three infectious agents as autoimmunity triggers in RA, namely Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans causes of periodontal disease (PD), and Epstein-Barr virus (EBV). P. gingivalis expresses arginine gingipains, that cleave proteins at the arginine residues, and peptidyl arginine deiminase (PPAD), which citrullinates arginine residues of proteins, thus forming neoantigens that lead to ACPA production...
2017: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29032929/binding-of-triazole-linked-galactosyl-arylsulfonamides-to-galectin-3-affects-trypanosoma-cruzi-cell-invasion
#3
Marcelo Fiori Marchiori, Thalita B Riul, Leandro Oliveira Bortot, Peterson Andrade, Getúlio G Junqueira, Giuseppina Foca, Nunzianna Doti, Menotti Ruvo, Marcelo Dias-Baruffi, Ivone Carvalho, Vanessa Leiria Campo
The synthesis of the O-3 triazole-linked galactosyl arylsulfonamides 1-7 as potential inhibitors of Trypanosoma cruzi cell invasion is described. These target compounds were synthesized by Cu(I)-catalysed azide-alkyne cycloaddition reaction ('click chemistry') between different azide arylsulfonamides and the alkyne-based sugar 3-O-propynyl-βGalOMe. Inhibition assays of T. cruzi cell invasion with compounds 1-7 showed reduced values of infection index (∼20) for compounds 3 and 5, bearing the corresponding 5-methylisoxazole and 2,4-dimethoxypyrimidine groups, which also presented higher binding affinities to galectin-3 (EC50 17-18 μM) in Corning Epic label-free assays...
September 30, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/29032899/th1-epitope-peptides-induce-protective-immunity-against-rickettsia-rickettsii-infection-in-c3h-hen-mice
#4
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/29029143/genome-wide-analysis-of-genetic-risk-factors-for-rheumatic-heart-disease-in-aboriginal-australians-provides-support-for-pathogenic-molecular-mimicry
#5
Lesley-Ann Gray, Heather A D'Antoine, Steven Y C Tong, Melita McKinnon, Dawn Bessarab, Ngaire Brown, Bo Reményi, Andrew Steer, Genevieve Syn, Jenefer M Blackwell, Michael Inouye, Jonathan R Carapetis
Background: Rheumatic heart disease (RHD) following Group A Streptococcus (GAS) infections is heritable and prevalent in Indigenous populations. Molecular mimicry between human and GAS proteins triggers pro-inflammatory cardiac valve-reactive T-cells. Methods: Genome-wide genetic analysis was undertaken in 1263 Aboriginal Australians (398 RHD cases; 865 controls). Single nucleotide polymorphisms (SNPs) were genotyped using Illumina HumanCoreExome BeadChips. Direct typing and imputation was used to fine-map the human leukocyte antigen (HLA) region...
September 26, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29025991/crystal-structure-of-a-tapbpr-mhc-i-complex-reveals-the-mechanism-of-peptide-editing-in-antigen-presentation
#6
Jiansheng Jiang, Kannan Natarajan, Lisa F Boyd, Giora I Morozov, Michael G Mage, David H Margulies
Central to CD8(+) T-cell mediated immunity is the recognition of peptide-major histocompatibility complex class I (pMHC-I) proteins displayed by antigen-presenting cells. Chaperone-mediated loading of high-affinity peptides onto MHC-I is a key step in the MHC-I antigen presentation pathway. However, the structure of MHC-I with a chaperone that facilitates peptide loading has not been determined. We report the crystal structure of MHC-I in complex with the peptide editor TAPBPR (TAP binding protein, related), a tapasin homolog...
October 12, 2017: Science
https://www.readbyqxmd.com/read/29025975/recognition-of-hyperacetylated-n-terminus-of-h2az-by-tbbdf2-from-trypanosoma-brucei
#7
Xiao Yang, Xuelei Wu, Jiahai Zhang, Xuecheng Zhang, Chao Xu, Shanhui Liao, Xiaoming Tu
Histone modification plays an important role in various biological processes, including gene expression regulation. Bromodomain, as one of histone readers, recognizes specifically the ε-N-lysine acetylation (KAc) of histone. Although the bromodomains and histone acetylation sites of Trypanosoma brucei ( T. brucei ), a lethal parasite responsible for sleeping sickness in human and nagana in cattle, have been identified, how acetylated histones are recognized by bromodomains is still unknown. Here, the bromodomain factor 2 (TbBDF2) from T...
October 12, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/29025906/comparative-profiling-of-hla-dr-and-hla-dq-associated-factor-viii-peptides-presented-by-monocyte-derived-dendritic-cells
#8
Ivan Peyron, Robin B Hartholt, Laura Pedró-Cos, Floris van Alphen, Anja Ten Brinke, Neubury Lardy, Sander Meijer, Jan Voorberg
The development of anti-factor VIII antibodies represents a major complication in the treatment of patients with hemophilia A. Generation of high affinity anti-factor VIII antibodies is dependent on help provided by CD4+ T cells that recognize factor VIII-derived peptides presented on class II major histocompatibility complex on the surface of antigen presenting cells. In order to identify the immune-dominant epitopes that can be presented to CD4+ T cells, we previously developed a mass-spectrometry based method to identify factor VIII derived peptides that are presented on human leucocyte antigen (HLA)-DR...
October 12, 2017: Haematologica
https://www.readbyqxmd.com/read/29023598/the-greenland-shark-somniosus-microcephalus-hemoglobins-and-ligand-binding-properties
#9
Roberta Russo, Daniela Giordano, Gianluca Paredi, Francesco Marchesani, Lisa Milazzo, Giovanna Altomonte, Pietro Del Canale, Stefania Abbruzzetti, Paolo Ascenzi, Guido di Prisco, Cristiano Viappiani, Angela Fago, Stefano Bruno, Giulietta Smulevich, Cinzia Verde
A large amount of data is currently available on the adaptive mechanisms of polar bony fish hemoglobins, but structural information on those of cartilaginous species is scarce. This study presents the first characterisation of the hemoglobin system of one of the longest-living vertebrate species (392 ± 120 years), the Arctic shark Somniosus microcephalus. Three major hemoglobins are found in its red blood cells and are made of two copies of the same α globin combined with two copies of three very similar β subunits...
2017: PloS One
https://www.readbyqxmd.com/read/29023112/design-of-leucine-rich-repeat-kinase-2-lrrk2-inhibitors-using-a-crystallographic-surrogate-derived-from-checkpoint-kinase-1-chk1
#10
Douglas S Williamson, Garrick P Smith, Pamela Acheson-Dossang, Simon T Bedford, Victoria Chell, I-Jen Chen, Justus C A Daechsel, Zoe Daniels, Laurent David, Pawel Dokurno, Morten Hentzer, Martin C Herzig, Roderick E Hubbard, Jonathan D Moore, James B Murray, Samantha Newland, Stuart C Ray, Terry Shaw, Allan E Surgenor, Lindsey Terry, Kenneth Thirstrup, Yikang Wang, Kenneth V Christensen
Mutations in leucine-rich repeat kinase 2 (LRRK2), such as G2019S, are associated with an increased risk of developing Parkinson's disease. Surrogates for the LRRK2 kinase domain based on checkpoint kinase 1 (CHK1) mutants were designed, expressed in insect cells infected with baculovirus, purified and crystallized. X-ray structures of the surrogates complexed with known LRRK2 inhibitors rationalized compound potency and selectivity. The CHK1 10-point mutant was preferred, following assessment of surrogate binding affinity with LRRK2 inhibitors...
October 12, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29018187/interconnected-subsets-of-memory-follicular-helper-t-cells-have-different-effector-functions
#11
Assia Asrir, Meryem Aloulou, Mylène Gador, Corine Pérals, Nicolas Fazilleau
Follicular helper T cells regulate high-affinity antibody production. Memory follicular helper T cells can be local in draining lymphoid organs and circulate in the blood, but the underlying mechanisms of this subdivision are unresolved. Here we show that both memory follicular helper T subsets sustain B-cell responses after reactivation. Local cells promote more plasma cell differentiation, whereas circulating cells promote more secondary germinal centers. In parallel, local memory B cells are homogeneous and programmed to become plasma cells, whereas circulating memory B cells are able to rediversify...
October 10, 2017: Nature Communications
https://www.readbyqxmd.com/read/28993513/dna-vaccination-by-electroporation-amplifies-broadly-cross-restricted-public-tcr-clonotypes-shared-with-hiv-controllers
#12
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...
October 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28992359/a-study-of-cdr3-loop-dynamics-reveals-distinct-mechanisms-of-peptide-recognition-by-t-cell-receptors-exhibiting-different-levels-of-cross-reactivity
#13
Yuko Tsuchiya, Yoshiki Namiuchi, Hiroshi Wako, Hiromichi Tsurui
T-cell receptors (TCRs) can productively interact with many different peptides bound within the major histocompatibility complex (MHC) binding groove. This property varies with the level of cross-reactivity of TCRs; some TCRs are particularly hyper cross-reactive while others exhibit greater specificity. To elucidate the mechanism behind these differences, we studied five TCRs, in complex with the same class II MHC (1A(b) )-peptide (3K), that are known to exhibit different levels of cross-reactivity. While these complexes have similar binding affinities, the interface areas between the TCR and peptide-MHC (pMHC) differ significantly...
October 9, 2017: Immunology
https://www.readbyqxmd.com/read/28991197/differential-proteome-analysis-of-extracellular-vesicles-from-breast-cancer-cell-lines-by-chaperone-affinity-enrichment
#14
Steven G Griffiths, Michelle T Cormier, Aled Clayton, Alan A Doucette
The complexity of human tissue fluid precludes timely identification of cancer biomarkers by immunoassay or mass spectrometry. An increasingly attractive strategy is to primarily enrich extracellular vesicles (EVs) released from cancer cells in an accelerated manner compared to normal cells. The Vn96 peptide was herein employed to recover a subset of EVs released into the media from cellular models of breast cancer. Vn96 has affinity for heat shock proteins (HSPs) decorating the surface of EVs. Reflecting their cells of origin, cancer EVs displayed discrete differences from those of normal phenotype...
October 8, 2017: Proteomes
https://www.readbyqxmd.com/read/28990569/-history-of-the-thymus-from-an-accident-of-evolution-to-the-programming-of-immunological-self-tolerance
#15
Vincent Geenen
This synthesis presents the most important disruptions of conceptions about the thymus since its discovery in Antique Greece. For centuries, the thymus was considered as a vestigial organ, and its role in T-lymphocyte differentiation has been proposed only in the 1960's. Most recent studies attribute to the thymus an essential and unique role in the programming of central immunological self-tolerance. The basal mechanism implicated in this function is the transcription in thymic epithelium of genes encoding precursors of self-antigens...
June 2017: Médecine Sciences: M/S
https://www.readbyqxmd.com/read/28990060/microrna-expression-profiling-of-intestinal-mucosa-tissue-predicts-multiple-crucial-regulatory-molecules-and-signaling-pathways-for-gut-barrier-dysfunction-of-aids-patients
#16
Yu Xu, Hua-Wei Wang, Hua-You Luo, Ruo Shu, Jia Liu, Liang Sun, Xue-Fei Han, Na Lin, Ting-Hua Wang, Yu-Jian Zeng, Kun-Hua Wang
Human immunodeficiency virus‑1 (HIV‑1) infection severely damages the gut‑associated lymphoid tissue (GALT), the immune system and the gut barrier, which leads to accelerating the disease progression for patients with acquired immune deficiency syndrome (AIDS). Dysregulation of microRNAs (miRNAs) may contribute to this process. However, few studies have investigated the importance of miRNAs in AIDS pathogenesis and progression. The whole miRNA profile of patients with HIV infection from southwest P.R...
October 4, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28989647/heterocyclic-boronic-acids-display-sialic-acid-selective-binding-in-a-hypoxic-tumor-relevant-acidic-environment
#17
A Matsumoto, A J Stephenson-Brown, T Khan, T Miyazawa, H Cabral, K Kataoka, Y Miyahara
Boronic acids are well known for their ability to reversibly interact with the diol groups found in sugars and glycoproteins. However, they are generally indiscriminate in their binding. Herein we describe the discovery of a group of heterocyclic boronic acids demonstrating unusually high affinity and selectivity for sialic acids (SAs or N-acetylneuraminic acid), which are sugar residues that are intimately linked with tumor growth and cancer progression. Remarkably, these interactions strengthen under the weakly acidic pH conditions associated with a hypoxic tumoral microenvironment...
September 1, 2017: Chemical Science
https://www.readbyqxmd.com/read/28987877/the-anthraquinone-emodin-inhibits-the-non-exported-fikk-kinase-from-plasmodium-falciparum
#18
Benjamin C Lin, Darcy R Harris, Lucy M D Kirkman, Astrid M Perez, Yiwen Qian, Janse T Schermerhorn, Min Y Hong, Dennis S Winston, Lingyin Xu, Alexander M Lieber, Matthew Hamilton, Gabriel S Brandt
The FIKK family of kinases is unique to parasites of the Apicomplexan order, which includes all malaria parasites. Plasmodium falciparum, the most virulent form of human malaria, has a family of 19 FIKK kinases, most of which are exported into the host red blood cell during malaria infection. Here, we confirm that FIKK 8 is a non-exported member of the FIKK kinase family. Through expression and purification of the recombinant kinase domain, we establish that emodin is a relatively high-affinity (IC50=2μM) inhibitor of PfFk8...
September 18, 2017: Bioorganic Chemistry
https://www.readbyqxmd.com/read/28987592/cathepsin-s-inhibition-suppresses-autoimmune-triggered-inflammatory-responses-in-macrophages
#19
Sophia Thanei, Michel Theron, Ana Patricia Silva, Bernhard Reis, Leonore Branco, Lucia Schirmbeck, Fabrice A Kolb, Wolfgang Haap, Thomas Schindler, Marten Trendelenburg
In several types of antigen-presenting cells (APCs), Cathepsin S (CatS) plays a crucial role in the regulation of MHC class II surface expression and consequently influences antigen (Ag) presentation of APCs to CD4(+) T cells. During the assembly of MHC class II-Ag peptide complexes, CatS cleaves the invariant chain p10 (Lip10) - a fragment of the MHC class II-associated invariant chain peptide. In this report, we used a selective, high-affinity CatS inhibitor to suppress the proteolytic activity of CatS in lymphoid and myeloid cells...
October 4, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28984845/site-directed-rna-editing-by-adenosine-deaminase-acting-on-rna-adar1-for-correction-of-the-genetic-code-in-gene-therapy
#20
T A Azad, S Bhakta, T Tsukahara
Site-directed RNA editing is an important technique for correcting gene sequences and ultimately tuning protein function. In this study, we engineered the deaminase domain of adenosine deaminase acting on RNA (ADAR1) and the MS2 system to target specific adenosines, with the goal of correcting G-to-A mutations at the RNA level. For this purpose, the ADAR1 deaminase domain was fused downstream of the RNA-binding protein MS2, which has affinity for the MS2 RNA. To direct editing to specific targets, we designed guide RNAs complementary to target RNAs...
October 6, 2017: Gene Therapy
keyword
keyword
16362
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"