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https://www.readbyqxmd.com/read/28077659/hiv-controllers-exhibit-enhanced-frequencies-of-mhc-class-ii-tetramer-gag-specific-cd4-t-cells-in-chronic-clade-c-hiv-1-infection
#1
Faatima Laher, Srinika Ranasinghe, Filippos Porichis, Nikoshia Mewalal, Karyn Pretorius, Nasreen Ismail, Søren Buus, Anette Stryhn, Mary Carrington, Bruce D Walker, Thumbi Ndung'u, Zaza M Ndhlovu
: Immune control of viral infections is heavily dependent on helper CD4(+) T cell function. However, understanding the contribution of HIV-specific CD4(+) T cell responses to immune protection against HIV-1, particularly in clade C infection remains incomplete. Recently, MHC class II tetramers have emerged as a powerful tool for interrogating antigen specific CD4(+) T cells without relying on effector functions. Here, we defined the MHC class II alleles for immunodominant Gag CD4(+) T cell epitopes in clade C virus infection, constructed MHC class II tetramers, and then used these to define the magnitude, function, and relation to viral load of HIV-specific CD4(+) T cell responses in a cohort of untreated HIV clade C infected persons...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28077649/tcr-clonotype-specific-differences-in-inhibitory-activity-of-hiv-1-cytotoxic-t-cell-clones-is-not-mediated-by-tcr-alone
#2
Nina C Flerin, Huabiao Chen, Tynisha D Glover, Pedro A Lamothe, Jian Hua Zheng, Justin W Fang, Zaza M Ndhlovu, Evan W Newell, Mark M Davis, Bruce D Walker, Harris Goldstein
: Functional analysis of T cell responses in HIV-infected individuals has indicated that virus-specific CD8(+) T cells with superior antiviral efficacy are well represented in HIV-1 controllers but are rare or absent in HIV-1 progessors. To define the role of individual TCR clonotypes in differential antiviral CD8(+) T cell function, we performed detailed functional and mass cytometric cluster analysis of multiple CD8(+) T cell clones recognizing the identical HLA-B*2705-restricted HIV-1 epitope KK10 (KRWIILGLNK)...
January 11, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28063951/transcriptomic-analysis-of-spleen-infected-with-infectious-salmon-anemia-virus-reveals-distinct-pattern-of-viral-replication-on-resistant-and-susceptible-atlantic-salmon-salmo-salar
#3
Phillip Dettleff, Thomas Moen, Nina Santi, Victor Martinez
The infectious salmon anemia virus (ISAv) produces a systemic infection in salmonids, causing large losses in salmon production. However, little is known regarding the mechanisms exerting disease resistance. In this paper, we perform an RNA-seq analysis in Atlantic salmon challenged with ISAv (using individuals coming from families that were highly susceptible or highly resistant to ISAv infection). We evaluated the differential expression of both host and ISAv genes in a target organ for the virus, i.e. the spleen...
January 4, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28060314/analysis-of-simian-immunodeficiency-virus-specific-cd8-t-cells-in-rhesus-macaques-by-peptide-mhc-i-tetramer-staining
#4
Lucas Gonzalez-Nieto, Aline Domingues, Michael Ricciardi, Martin J Gutman, Helen S Maxwell, Nuria Pedreño-Lopez, Varian Bailey, Diogo M Magnani, Mauricio A Martins
Peptide-major histocompatibility complex class I (pMHC-I) tetramers have been an invaluable tool to study CD8(+) T-cell responses. Because these reagents directly bind to T-cell receptors on the surface of CD8(+) T-lymphocytes, fluorochrome-labeled pMHC-I tetramers enable the accurate detection of antigen (Ag)-specific CD8(+) T-cells without the need for in vitro re-stimulation. Moreover, when combined with multi-color flow cytometry, pMHC-I tetramer staining can reveal key aspects of Ag-specific CD8(+) T-cells, including differentiation stage, memory phenotype, and activation status...
December 23, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28060015/ifn-%C3%AE-augments-nk-mediated-antibody-dependent-cellular-cytotoxicity-adcc-of-hiv-1-infected-autologous-cd4-t-cells-regardless-of-mhc-i-downregulation
#5
Costin Tomescu, Pablo Tebas, Luis J Montaner
DESIGN: We have previously shown that IFN-α stimulation augments direct NK cell lysis of autologous CD4 primary T cells infected with certain HIV-1 isolates based upon MHC-I downregulation capacity. Here, we investigated if Antibody Dependent Cellular Cytotoxicity (ADCC) could trigger lysis of HIV-1 isolates that were resistant to direct NK lysis and if IFN-α pre-stimulation of NK cells could further enhance ADCC. METHODS: Using broadly neutralizing monoclonal antibodies against gp120 (VRC01 or PGV04) or plasma from HIV-1 infected subjects (ART-suppressed or Elite Controller) to trigger ADCC, we measured NK cell chromium release cytotoxicity against HIV-1 infected autologous CD4 primary T cells and NK cell CD107a degranulation against gp120-coated CD4 T cells...
January 4, 2017: AIDS
https://www.readbyqxmd.com/read/28051183/hiv-1-env-associates-with-hla-c-free-chains-at-the-cell-membrane-modulating-viral-infectivity
#6
Michela Serena, Francesca Parolini, Priscilla Biswas, Francesca Sironi, Almudena Blanco Miranda, Elisa Zoratti, Maria Teresa Scupoli, Serena Ziglio, Agustin Valenzuela-Fernandez, Davide Gibellini, Maria Grazia Romanelli, Antonio Siccardi, Mauro Malnati, Alberto Beretta, Donato Zipeto
HLA-C has been demonstrated to associate with HIV-1 envelope glycoprotein (Env). Virions lacking HLA-C have reduced infectivity and increased susceptibility to neutralizing antibodies. Like all others MHC-I molecules, HLA-C requires β2-microglobulin (β2m) for appropriate folding and expression on the cell membrane but this association is weaker, thus generating HLA-C free-chains on the cell surface. In this study, we deepen the understanding of HLA-C and Env association by showing that HIV-1 specifically increases the amount of HLA-C free chains, not bound to β2m, on the membrane of infected cells...
January 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/27941629/the-telomerase-derived-anticancer-peptide-vaccine-gv1001-as-an-extracellular-heat-shock-protein-mediated-cell-penetrating-peptide
#7
REVIEW
Hong Kim, Eun-Hye Seo, Seung-Hyun Lee, Bum-Joon Kim
Cell-penetrating peptides (CPPs), which can facilitate the transport of molecular cargo across the plasma membrane, have become important tools in promoting the cellular delivery of macromolecules. GV1001, a peptide derived from a reverse-transcriptase subunit of telomerase (hTERT) and developed as a vaccine against various cancers, reportedly has unexpected CPP properties. Unlike typical CPPs, such as the HIV-1 TAT peptide, GV1001 enabled the cytosolic delivery of macromolecules such as proteins, DNA and siRNA via extracellular heat shock protein 90 (eHSP90) and 70 (eHSP70) complexes...
December 7, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27936416/antigen-recognition-triggered-drug-delivery-mediated-by-nanocapsule-functionalized-cytotoxic-t-cells
#8
R Brad Jones, Stephanie Mueller, Sudha Kumari, Vlad Vrbanac, Shy Genel, Andrew M Tager, Todd M Allen, Bruce D Walker, Darrell J Irvine
Cytotoxic T-Lymphocytes (CTLs) kill pathogen-infected or transformed cells following interaction of their T-cell receptors (TCRs) with foreign (e.g. virus-derived) peptides bound to MHC-I molecules on the target cell. TCR binding triggers CTLs to secrete perforin, which forms pores in the target cell membrane, promoting target death. Here, we show that by conjugating drug-loaded lipid nanoparticles to the surface of CTLs, their lytic machinery can be co-opted to lyse the cell-bound drug carrier, providing triggered release of drug cargo upon target cell recognition...
February 2017: Biomaterials
https://www.readbyqxmd.com/read/27905838/engineering-hiv-specific-immunity-with-chimeric-antigen-receptors
#9
Scott G Kitchen, Jerome A Zack
HIV remains a highly important public health and clinical issue despite many recent advances in attempting to develop a cure, which has remained elusive for most people infected with HIV. HIV disease can be controlled with pharmacologic therapies; however, these treatments are expensive, may have severe side effects, and are not curative. Consequently, an improved means to control or eliminate HIV replication is needed. Cytotoxic T lymphocytes (CTLs) play a critical role in controlling viral replication and are an important part in the ability of the immune response to eradicate most viral infections...
December 2016: AIDS Patient Care and STDs
https://www.readbyqxmd.com/read/27810495/psoriasis-risk-snps-and-their-association-with-hiv-1-control
#10
Joanne Nititham, Rashmi Gupta, Xue Zeng, Wendy Hartogensis, Douglas F Nixon, Steven G Deeks, Frederick M Hecht, Wilson Liao
Human evolution has resulted in selection for genetic polymorphisms beneficial in the defense against pathogens. However, such polymorphisms may have the potential to heighten the risk of autoimmune disease. Here, we investigated whether psoriasis-associated single nucleotide polymorphisms influence host control of HIV-1 infection. We studied psoriasis and viral immune response variants in three HIV-positive cohorts: (1) HIV-1 controllers and non-controllers in the Study of the Consequences of the Protease Inhibitor Era (SCOPE) cohort (n=366), (2) Individuals with primary HIV infection in the Options cohort (n=675), and (3) HIV-positive injection drug users from the Urban Health Study (UHS) (n=987)...
October 31, 2016: Human Immunology
https://www.readbyqxmd.com/read/27787793/phenotypic-and-functional-analysis-of-antigen-specific-t-cell-exhaustion
#11
Kristin L Boswell, Takuya Yamamoto
In some cancers and chronic infections exhausted T cells increase their expression of inhibitory receptors and demonstrate an impaired ability to produce cytokines and to proliferate. Immunological techniques such as MHC class I tetramer staining, intracellular cytokine staining, and CFSE dilution can be used to determine the memory status, inhibitory receptor expression, cytokine production, and proliferative capacity of antigen-specific CD8(+) T cells. Here, we describe approaches to define the inhibitory receptor expression, cytokine production, and proliferative capacity of antigen-specific CD8(+) T cells from HIV-infected and CMV-infected donors by using polychromatic flow cytometry...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27760342/antiviral-cd8-t-cells-restricted-by-human-leukocyte-antigen-class-ii-exist-during-natural-hiv-infection-and-exhibit-clonal-expansion
#12
Srinika Ranasinghe, Pedro A Lamothe, Damien Z Soghoian, Samuel W Kazer, Michael B Cole, Alex K Shalek, Nir Yosef, R Brad Jones, Faith Donaghey, Chioma Nwonu, Priya Jani, Gina M Clayton, Frances Crawford, Janice White, Alana Montoya, Karen Power, Todd M Allen, Hendrik Streeck, Daniel E Kaufmann, Louis J Picker, John W Kappler, Bruce D Walker
CD8(+) T cell recognition of virus-infected cells is characteristically restricted by major histocompatibility complex (MHC) class I, although rare examples of MHC class II restriction have been reported in Cd4-deficient mice and a macaque SIV vaccine trial using a recombinant cytomegalovirus vector. Here, we demonstrate the presence of human leukocyte antigen (HLA) class II-restricted CD8(+) T cell responses with antiviral properties in a small subset of HIV-infected individuals. In these individuals, T cell receptor β (TCRβ) analysis revealed that class II-restricted CD8(+) T cells underwent clonal expansion and mediated killing of HIV-infected cells...
October 18, 2016: Immunity
https://www.readbyqxmd.com/read/27760334/class-ii-restricted-cd8s-new-lessons-violate-old-paradigms
#13
Stephen A Migueles, Mark Connors
CD8(+) T cells that recognize peptides presented by MHC class II molecules have been observed in a macaque SIV vaccine model. A new study by Ranasinghe et al. (2016) shows that virus-specific class-II-restricted CD8(+) T cells can be found in some HIV-infected patients.
October 18, 2016: Immunity
https://www.readbyqxmd.com/read/27734954/pseudo-mannosylated-dc-sign-ligands-as-immunomodulants
#14
Angela Berzi, Stefania Ordanini, Ben Joosten, Daria Trabattoni, Alessandra Cambi, Anna Bernardi, Mario Clerici
DC-SIGN, a C-type lectin mainly expressed by DCs, mediates antigen uptake and can induce specific immune responses, depending on the ligand involved. Owing to these properties, DC-SIGN is an attracting target for approaches aimed at tailoring the immune response towards specific immunologic outcomes. A multivalent DC-SIGN ligand (Polyman26), containing at its core a fluorescent "rod-like" spacer and able to inhibit DC-SIGN mediated HIV infection in nanomolar concentration, has been recently developed by our group...
October 13, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27729588/the-importance-of-understanding-mhc-i-diversity-in-nonhuman-primate-models-of-human-infectious-diseases
#15
Nicholas J Maness
Decades of research, including the 1996 Nobel Prize in Medicine, confirm the evolutionary and immunological importance of CD8 T lymphocytes (TCD8+) that target peptides bound by the highly variable major histocompatibility complex class I (MHC-I) proteins. However, their perceived importance has varied dramatically over the past decade. Regardless, there remains myriad reasons to consider the diversity of MHC-I alleles and the TCD8+ that target them as enormously important in infectious disease research. Thus, understanding these molecules in the best animal models of human disease could be a necessity for optimizing the translational potential of these models...
October 11, 2016: Toxicologic Pathology
https://www.readbyqxmd.com/read/27681150/psychosocial-well-being-of-people-living-with-hiv-and-the-community-before-and-after-a-hiv-stigma-reduction-community-hub-network-intervention
#16
Catharina D Prinsloo, Minrie Greeff, Annamarie Kruger, Suria Ellis
The purpose of the research was to determine whether an HIV stigma-reduction community "hub" network intervention in a South African urban area would bring about a difference in the psychosocial well-being of people living with HIV (PLWH), as well as their community (living in the same municipal ward). A single case pre-test post-test design was implemented. The sample for this study included 62 PLWH who were selected through accessibility sampling and 570 community members who were selected through random voluntary sampling...
September 2016: African Journal of AIDS Research: AJAR
https://www.readbyqxmd.com/read/27633333/the-role-of-mucosal-associated-invariant-t-cells-in-infectious-diseases
#17
REVIEW
Emily B Wong, Thumbi Ndung'u, Victoria O Kasprowicz
Mucosal-associated invariant T (MAIT) cells are donor-unrestricted lymphocytes that are surprisingly abundant in humans, representing 1-10% of circulating T cells and further enriched in mucosal tissues. MAIT cells recognize and are activated by small molecule ligands produced by microbes and presented by MR1, a highly conserved MHC-related antigen-presenting protein that is ubiquitously expressed in human cells. Increasing evidence suggests that MAIT cells play a protective role in anti-bacterial immunity at mucosal interfaces...
January 2017: Immunology
https://www.readbyqxmd.com/read/27613235/type-i-interferon-responses-are-impaired-in-latently-hiv-infected-cells
#18
Nischal Ranganath, Teslin S Sandstrom, Saleh Fadel, Sandra C Côté, Jonathan B Angel
BACKGROUND: The latent HIV-1 reservoir represents the primary barrier to the eradication of HIV-1 infection. The design of novel reservoir-clearance strategies, however, is impeded in part by the inability to distinguish latently HIV-infected cells from uninfected cells. Significant impairment of the type I interferon (IFN-I) response is observed during productive HIV-1 infection. Although this remains poorly described in the context of latent HIV-1 infection, presence of potential defects may serve as a novel therapeutic target...
September 9, 2016: Retrovirology
https://www.readbyqxmd.com/read/27551741/reduction-sensitive-peg-hydrogels-for-codelivery-of-antigen-and-adjuvant-to-induce-potent-ctls
#19
Chintan H Kapadia, Shaomin Tian, Jillian L Perry, J Christopher Luft, Joseph M DeSimone
Educating our immune system via vaccination is an attractive approach to combat infectious diseases. Eliciting antigen specific cytotoxic T cells (CTLs), CD8(+) effector T cells, is essential in controlling intracellular infectious diseases such as influenza (Flu), tuberculosis (TB), hepatitis, and HIV/AIDS, as well as tumors. However, vaccination utilizing subunit peptides to elicit a potent CD8(+) T cell response with antigenic peptides is typically ineffective due to poor immunogenicity. Here we have engineered a reduction sensitive nanoparticle (NP) based subunit vaccine for intracellular delivery of an antigenic peptide and immunostimulatory adjuvant...
October 3, 2016: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/27525406/-viral-superantigens
#20
Dürdal Us
Superantigens (SAgs) are microbial proteins produced by various microorganisms that elicit excessive and strong stimulation of T cells via an unconventional mechanism. They cause polyclonal activation of T cells in a non-specific manner, by binding to a particular variable-beta (Vβ) chain of T-cell receptor (TCR) and MHC class II molecule, in unprocessed form and outside of peptide-binding cleft, forming a bridge between the antigen presenting cell and the T cell. SAgs are classified into three groups, namely 1) exogenous (soluble proteins and exotoxins secreted by microorganisms), 2) endogenous (transmembrane proteins encoded by viruses which are integrated into the genome) and 3) B-cell SAgs (proteins which stimulate predominantly B cells)...
July 2016: Mikrobiyoloji Bülteni
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