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https://www.readbyqxmd.com/read/28446731/the-antigenic-identity-of-human-class-i-mhc-phosphopeptides-is-critically-dependent-upon-phosphorylation-status
#1
Fiyaz Mohammed, Daniel H Stones, Angela L Zarling, Carrie R Willcox, Jeffrey Shabanowitz, Kara L Cummings, Donald F Hunt, Mark Cobbold, Victor H Engelhard, Benjamin E Willcox
Dysregulated post-translational modification provides a source of altered self-antigens that can stimulate immune responses in autoimmunity, inflammation, and cancer. In recent years, phosphorylated peptides have emerged as a group of tumour-associated antigens presented by MHC molecules and recognised by T cells, and represent promising candidates for cancer immunotherapy. However, the impact of phosphorylation on the antigenic identity of phosphopeptide epitopes is unclear. Here we examined this by determining structures of MHC-bound phosphopeptides bearing canonical position 4-phosphorylations in the presence and absence of their phosphate moiety, and examining phosphopeptide recognition by the T cell receptor (TCR)...
April 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445138/killer-cell-immunoglobulin-like-receptor-2dl4-is-expressed-in-and-suppresses-the-cell-growth-of-langerhans-cell-histiocytosis
#2
Yusuke Takei, Chiyuki Ueshima, Tatsuki R Kataoka, Masahiro Hirata, Akihiko Sugimoto, Mariyo Rokutan-Kurata, Koki Moriyoshi, Kazuo Ono, Ichiro Murakami, Sanju Iwamoto, Hironori Haga
Killer cell immunoglobulin-like receptor (KIR) 2DL4 (CD158d) is a receptor for human leukocyte antigen-G. The function of KIR2DL4 has been reported in human natural killer cell lymphoma and mastocytosis, but not in Langerhans cell histiocytosis (LCH). Herein, we examined the expression and function of KIR2DL4 in LCHs. In pathological specimens, 27 of 36 LCH cases (75.0%) were immunohistochemically positive for KIR2DL4. Its expression was independent of age, gender, location, multi- or single-system, and the status of BRAFV600E immunostaining...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28443094/serum-igg-antibodies-from-pregnant-women-reacting-to-mimotopes-of-simian-virus-40-large-t-antigen-the-viral-oncoprotein
#3
Elisa Mazzoni, Mariantonietta Di Stefano, Josè R Fiore, Federica Destro, Marco Manfrini, John Charles Rotondo, Maria V Casali, Fortunato Vesce, Pantaleo Greco, Gennaro Scutiero, Fernanda Martini, Mauro G Tognon
Simian virus 40 (SV40) large T antigen (LT) coding sequences were revealed in different human samples, whereas SV40 antibodies (Ab) were detected in human sera of cancer patients and healthy individuals, although with a lower prevalence. Previous studies carried out by the neutralization assay gave a SV40 seroprevalence, in the general population, up to 8%, although higher rates, 12%, were detected in kidney transplant children, in a group of HIV-positive patients, and in healthy females. In this study, serum samples from pregnant women, together with those from non-pregnant women, were analyzed to check the prevalence of IgG Ab reacting to SV40 LT antigens...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28440548/contact-sensitizers-trigger-human-cd1-autoreactive-t-cell-responses
#4
Richard J Betts, Adrijana Perkovic, Subhashree Mahapatra, Aurélia Del Bufalo, Kaddy Camara, Amy R Howell, Silvia Martinozzi Teissier, Gennaro De Libero, Lucia Mori
Allergic contact dermatitis is a primarily T-cell-mediated inflammatory skin disease induced by exposure to small molecular-weight haptens, which covalently bind to proteins. The abundance of cutaneous T cells that recognize CD1a antigen-presenting molecules raises the possibility that MHC-independent antigen presentation may be relevant in some hapten-driven immune responses. Here we examine the ability of contact sensitizers to influence CD1-restricted immunity. Exposure of human antigen-presenting cells such as monocyte-derived dendritic cells and THP-1 cells to the prototypical contact sensitizer dinitrochlorobenzene potentiated the response of CD1a- and CD1d-autoreactive T cells, which released a vast array of cytokines in a CD1- and TCR-dependent manner...
April 25, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28440342/significant-variation-between-snp-based-hla-imputations-in-diverse-populations-the-last-mile-is-the-hardest
#5
D J Pappas, A Lizee, V Paunic, K R Beutner, A Motyer, D Vukcevic, S Leslie, J Biesiada, J Meller, K D Taylor, X Zheng, L P Zhao, P-A Gourraud, J A Hollenbach, S J Mack, M Maiers
Four single nucleotide polymorphism (SNP)-based human leukocyte antigen (HLA) imputation methods (e-HLA, HIBAG, HLA*IMP:02 and MAGPrediction) were trained using 1000 Genomes SNP and HLA genotypes and assessed for their ability to accurately impute molecular HLA-A, -B, -C and -DRB1 genotypes in the Human Genome Diversity Project cell panel. Imputation concordance was high (>89%) across all methods for both HLA-A and HLA-C, but HLA-B and HLA-DRB1 proved generally difficult to impute. Overall, <27.8% of subjects were correctly imputed for all HLA loci by any method...
April 25, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28439930/detection-and-identification-of-platelet-antibodies-using-a-sensitive-multiplex-assay-system-platelet-antibody-bead-array
#6
Krista Metzner, Julie Bauer, Heather Ponzi, Allison Ujcich, Brian R Curtis
BACKGROUND: Tests for platelet-specific antibodies are important in the diagnosis of immune platelet disorders. Monoclonal antibody glycoprotein capture assays have been the gold standards in platelet antibody detection for almost 30 years. However, such assays are complex and cumbersome to perform, which limits their routine use. We report the performance of a newly developed, easy to perform platelet antibody bead array (PABA) for the detection of platelet-specific antibodies. STUDY DESIGN AND METHODS: PABA is the equivalent of the monoclonal antigen capture enzyme-linked immunosorbent assay (ELISA) (MACE) on a bead and instead with fluorescent detection of immunoglobulin (Ig)G platelet antibodies by Luminex...
April 25, 2017: Transfusion
https://www.readbyqxmd.com/read/28439008/interaction-of-proliferating-cell-nuclear-antigen-with-pms2-is-required-for-mutl%C3%AE-activation-and-function-in-mismatch-repair
#7
Jochen Genschel, Lyudmila Y Kadyrova, Ravi R Iyer, Basanta K Dahal, Farid A Kadyrov, Paul Modrich
Eukaryotic MutLα (mammalian MLH1-PMS2 heterodimer; MLH1-PMS1 in yeast) functions in early steps of mismatch repair as a latent endonuclease that requires a mismatch, MutSα/β, and DNA-loaded proliferating cell nuclear antigen (PCNA) for activation. We show here that human PCNA and MutLα interact specifically but weakly in solution to form a complex of approximately 1:1 stoichiometry that depends on PCNA interaction with the C-terminal endonuclease domain of the MutLα PMS2 subunit. Amino acid substitution mutations within a PMS2 C-terminal (721)QRLIAP motif attenuate or abolish human MutLα interaction with PCNA, as well as PCNA-dependent activation of MutLα endonuclease, PCNA- and DNA-dependent activation of MutLα ATPase, and MutLα function in in vitro mismatch repair...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438110/temporal-progression-of-lesions-in-guinea-pigs-infected-with-lassa-virus
#8
T M Bell, C I Shaia, J J Bearss, M E Mattix, K A Koistinen, S P Honnold, X Zeng, C D Blancett, G C Donnelly, J D Shamblin, E R Wilkinson, K A Cashman
Lassa virus (LASV) infection causes an acute, multisystemic viral hemorrhagic fever that annually infects an estimated 100 000 to 300 000 persons in West Africa. This pathogenesis study evaluated the temporal progression of disease in guinea pigs following aerosol and subcutaneous inoculation of the Josiah strain of LASV as well as the usefulness of Strain 13 guinea pigs as an animal model for Lassa fever. After experimental infection, guinea pigs ( Cavia porcellus; n = 67) were serially sampled to evaluate the temporal progression of infection, gross and histologic lesions, and serum chemistry and hematologic changes...
May 2017: Veterinary Pathology
https://www.readbyqxmd.com/read/28436963/a-sting-activating-nanovaccine-for-cancer-immunotherapy
#9
Min Luo, Hua Wang, Zhaohui Wang, Haocheng Cai, Zhigang Lu, Yang Li, Mingjian Du, Gang Huang, Chensu Wang, Xiang Chen, Matthew R Porembka, Jayanthi Lea, Arthur E Frankel, Yang-Xin Fu, Zhijian J Chen, Jinming Gao
The generation of tumour-specific T cells is critically important for cancer immunotherapy. A major challenge in achieving a robust T-cell response is the spatiotemporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we report a minimalist nanovaccine, comprising a simple physical mixture of an antigen and a synthetic polymeric nanoparticle, PC7A NP, which generates a strong cytotoxic T-cell response with low systemic cytokine expression. Mechanistically, the PC7A NP achieves efficient cytosolic delivery of tumour antigens to antigen-presenting cells in draining lymph nodes, leading to increased surface presentation while simultaneously activating type I interferon-stimulated genes...
April 24, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28431981/ventricular-assist-device-elicits-serum-natural-igg-that-correlates-with-the-development-of-primary-graft-dysfunction-following-heart-transplantation
#10
Sarah B See, Kevin J Clerkin, Peter J Kennel, Feifan Zhang, Matthew P Weber, Kortney J Rogers, Debanjana Chatterjee, Elena R Vasilescu, George Vlad, Yoshifumi Naka, Susan W Restaino, Maryjane A Farr, Veli K Topkara, Paolo C Colombo, Donna M Mancini, P Christian Schulze, Bruce Levin, Emmanuel Zorn
BACKGROUND: Pre-transplant sensitization is a limiting factor in solid-organ transplantation. In heart transplants, ventricular assist device (VAD) implantation has been associated with sensitization to human leukocyte antigens (HLA). The effect of VAD on non-HLA antibodies is unclear. We have previously shown that polyreactive natural antibodies (Nabs) contribute to pre-sensitization in kidney allograft recipients. Here we assessed generation of Nabs after VAD implantation in pre-transplant sera and examined their contribution to cardiac allograft outcome...
March 24, 2017: Journal of Heart and Lung Transplantation
https://www.readbyqxmd.com/read/28427948/comprehensive-characterization-of-humoral-correlates-of-human-immunodeficiency-virus-1-superinfection-acquisition-in-high-risk-kenyan-women
#11
Keshet Ronen, Adam S Dingens, Susan M Graham, Walter Jaoko, Kishor Mandaliya, R Scott McClelland, Julie Overbaugh
HIV-1 superinfection, in which an infected individual acquires a second HIV-1 infection from a different partner, is one of the only settings in which HIV acquisition occurs in the context of a pre-existing immune response to natural HIV infection. There is evidence that initial infection provides some protection from superinfection, particularly after 6months of initial infection, when development of broad immunity occurs. Comparison of the immune response of superinfected individuals at the time of superinfection acquisition to that of individuals who remain singly infected despite continued exposure can shed light on immune correlates of HIV acquisition to inform prophylactic vaccine design...
April 2017: EBioMedicine
https://www.readbyqxmd.com/read/28427432/anti-human-platelet-antigen-hpa-1a-antibodies-may-affect-trophoblast-functions-crucial-for-placental-development-a-laboratory-study-using-an-in-vitro-model
#12
Mariana Eksteen, Gøril Heide, Heidi Tiller, Yan Zhou, Nora Hersoug Nedberg, Inigo Martinez-Zubiaurre, Anne Husebekk, Bjørn R Skogen, Tor B Stuge, Mette Kjær
BACKGROUND: Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a bleeding disorder caused by maternal antibodies against paternal human platelet antigens (HPAs) on fetal platelets. Antibodies against HPA-1a are accountable for the majority of FNAIT cases. We have previously shown that high levels of maternal anti-HPA-1a antibodies are associated with clinically significant reduced birth weight in newborn boys. Chronic inflammatory placental lesions are associated with increased risk of reduced birth weight and have previously been reported in connection with FNAIT pregnancies...
April 21, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28424684/modulation-of-human-leukocyte-antigen-c-by-human-cytomegalovirus-stimulates-kir2ds1-recognition-by-natural-killer-cells
#13
Kattria van der Ploeg, Chiwen Chang, Martin A Ivarsson, Ashley Moffett, Mark R Wills, John Trowsdale
The interaction of inhibitory killer cell Ig-like receptors (KIRs) with human leukocyte antigen (HLA) class I molecules has been characterized in detail. By contrast, activating members of the KIR family, although closely related to inhibitory KIRs, appear to interact weakly, if at all, with HLA class I. KIR2DS1 is the best studied activating KIR and it interacts with C2 group HLA-C (C2-HLA-C) in some assays, but not as strongly as KIR2DL1. We used a mouse 2B4 cell reporter system, which carries NFAT-green fluorescent protein with KIR2DS1 and a modified DAP12 adaptor protein...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28421694/molecular-engineering-and-plant-expression-of-an-immunoglobulin-heavy-chain-scaffold-for-delivery-of-a-dengue-vaccine-candidate
#14
Mi-Young Kim, Craig Van Dolleweerd, Alastair Copland, Matthew John Paul, Sven Hofmann, Gina R Webster, Emily Julik, Ivonne Ceballos-Olvera, Jorge Reyes-Del Valle, Moon-Sik Yang, Yong-Suk Jang, Rajko Reljic, Julian K Ma
In order to enhance vaccine uptake by the immune cells in vivo, molecular engineering approach was employed to construct a Polymeric Immunoglobulin G Scaffold (PIGS) that incorporates multiple copies of an antigen and targets the Fc gamma receptors on antigen-presenting cells. These self-adjuvanting immunogens were tested in the context of dengue infection, for which there is currently no globally licensed vaccine yet. Thus, the consensus domain III sequence (cEDIII) of dengue glycoprotein E was incorporated into PIGS and expressed in both tobacco plants and Chinese Ovary Hamster cells...
April 19, 2017: Plant Biotechnology Journal
https://www.readbyqxmd.com/read/28419492/expression-and-trafficking-of-mhc-related-protein-1-mr1
#15
REVIEW
R Lamichhane, J E Ussher
MHC related protein 1 (MR1) is a non-polymorphic MHC class IB antigen presenting molecule that is the restricting molecule for mucosal associated invariant T (MAIT) cells, a prominent population of innate-like antibacterial T cells. The MAIT cell-MR1 axis represents a new paradigm in antigen presentation, with the MR1 ligand derived from vitamin B compounds or their metabolic precursors. Many bacteria and some fungi produce the activating ligand for MR1. In evolution, MR1 is highly conserved in most, but not all, mammals...
April 17, 2017: Immunology
https://www.readbyqxmd.com/read/28418011/more-than-25-years-of-genetic-studies-of-clozapine-induced-agranulocytosis
#16
REVIEW
S A J de With, S L Pulit, W G Staal, R S Kahn, R A Ophoff
Clozapine is one of the most effective atypical antipsychotic drugs prescribed to patients with treatment-resistant schizophrenia. Approximately 1% of patients experience potential life-threatening adverse effects in the form of agranulocytosis, greatly hindering its applicability in clinical practice. The etiology of clozapine-induced agranulocytosis (CIA) remains unclear, but is thought to be a heritable trait. We reviewed the genetic studies of CIA published thus far. One recurrent finding from early candidate gene study to more recent genome-wide analysis is that of the involvement of human leukocyte antigen locus...
April 18, 2017: Pharmacogenomics Journal
https://www.readbyqxmd.com/read/28414815/isolation-of-human-explant-derived-cardiac-stem-cells-from-cryopreserved-heart-tissue
#17
Robyn Jackson, Seth Mount, Bin Ye, Audrey E Mayfield, Vincent Chan, Munir Boodhwani, Ross A Davies, Haissam Haddad, Darryl R Davis
The value of preserving high quality bio specimens for fundamental research is significant as linking cellular and molecular changes to clinical and epidemiological data has fueled many recent advances in medicine. Unfortunately, storage of traditional biospecimens is limited to fixed samples or isolated genetic material. Here, we report the effect of cryopreservation of routine myocardial biopsies on explant derived cardiac stem cell (EDC) culture outcomes. We demonstrate that immediate cryopreservation or delayed cryopreservation after suspension within cardioplegia for 12 hours did not alter EDC yields, proliferative capacity, antigenic phenotype or paracrine signature...
2017: PloS One
https://www.readbyqxmd.com/read/28414303/development-of-potent-class-ii-transactivator-gene-delivery-systems-capable-of-inducing-de-novo-mhc-ii-expression-in-human-cells-in-vitro-and-ex-vivo
#18
M de Lucena Palma, P Duangkhae, B Douradinha, I F T Viana, P O Rigato, R Dhalia, R B Mailliard, S M Barratt-Boyes, E J M do Nascimento, T M Oshiro, A J da Silva Duarte, E T de A Marques
Class II Transactivator (CIITA) induces transcription of MHC II genes and can potentially be used to improve genetic immunotherapies by converting non-immune cells into cells capable of presenting antigens to CD4(+) T cells. However, CIITA expression is tightly controlled and it remains unclear whether distinct non-immune cells differ in this transactivator regulation. Here we describe the development of gene delivery systems capable of promoting the efficient CIITA expression in non-immune cell lines and in primary human cells of an ex vivo skin explant model...
April 17, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28413020/%C3%AE-%C3%AE-t-cells-and-b-cells
#19
REVIEW
Willi K Born, Yafei Huang, R Lee Reinhardt, Hua Huang, Deming Sun, Rebecca L O'Brien
γδ T cells constitute the third arm of a tripartite adaptive immune system in jawed vertebrates, besides αβ T cells and B cells. Like the other two lymphocyte-types, they express diverse antigen receptors, capable of specific ligand recognition. Functionally, γδ T cells represent a system of differentiated subsets, sometimes engaged in cross-regulation, which ultimately determines their effect on other components of the immune system, including B cells and antibodies. γδ T cells are capable of providing help to B cells in antibody production...
2017: Advances in Immunology
https://www.readbyqxmd.com/read/28412927/widespread-subcutaneous-necrosis-in-spotted-fever-group-rickettsioses-from-the-coastal-belt-of-sri-lanka-a-case-report
#20
Nathasha Luke, Hasini Munasinghe, Lakshmi Balasooriya, Ranjan Premaratna
BACKGROUND: Spotted fever group rickettsioses (SFGR) transmitted mostly by ticks are increasingly discovered around the World and some of them are either re-emerging or emerging in Sri Lanka. Accidental human infections caused by these vector borne zoonotic diseases generally give rise to nonspecific acute febrile illnesses which can be complicated by multi organ involvement carrying high morbidity and mortality. Nonspecific clinical features and non-availability of early diagnostic facilities are known to result in delay in the diagnosis of rickettsial infections...
April 17, 2017: BMC Infectious Diseases
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