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https://www.readbyqxmd.com/read/28228759/interleukin-35-producing-cd8%C3%AE-dendritic-cells-acquire-a-tolerogenic-state-and-regulate-t-cell-function
#1
Sergio Haller, Anaïs Duval, Romain Migliorini, Mathias Stevanin, Vanessa Mack, Hans Acha-Orbea
Dendritic cells (DCs) play a central role in shaping immunogenic as well as tolerogenic adaptive immune responses and thereby dictate the outcome of adaptive immunity. Here, we report the generation of a CD8α(+) DC line constitutively secreting the tolerogenic cytokine interleukin (IL)-35. IL-35 secretion led to impaired CD4(+) and CD8(+) T lymphocyte proliferation and interfered with their function in vitro and also in vivo. IL-35 was furthermore found to induce a tolerogenic phenotype on CD8α(+) DCs, characterized by the upregulation of CD11b, downregulation of MHC class II, a reduced costimulatory potential as well as production of the immunomodulatory molecule IL-10...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28228754/proofreading-of-peptide-mhc-complexes-through-dynamic-multivalent-interactions
#2
REVIEW
Christoph Thomas, Robert Tampé
The adaptive immune system is able to detect and destroy cells that are malignantly transformed or infected by intracellular pathogens. Specific immune responses against these cells are elicited by antigenic peptides that are presented on major histocompatibility complex class I (MHC I) molecules and recognized by cytotoxic T lymphocytes at the cell surface. Since these MHC I-presented peptides are generated in the cytosol by proteasomal protein degradation, they can be metaphorically described as a window providing immune cells with insights into the state of the cellular proteome...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28218747/mhc-i-peptides-get-out-of-the-groove-and-enable-a-novel-mechanism-of-hiv-1-escape
#3
Phillip Pymm, Patricia T Illing, Sri H Ramarathinam, Geraldine M O'Connor, Victoria A Hughes, Corinne Hitchen, David A Price, Bosco K Ho, Daniel W McVicar, Andrew G Brooks, Anthony W Purcell, Jamie Rossjohn, Julian P Vivian
Major histocompatibility complex class I (MHC-I) molecules play a crucial role in immunity by capturing peptides for presentation to T cells and natural killer (NK) cells. The peptide termini are tethered within the MHC-I antigen-binding groove, but it is unknown whether other presentation modes occur. Here we show that 20% of the HLA-B*57:01 peptide repertoire comprises N-terminally extended sets characterized by a common motif at position 1 (P1) to P2. Structures of HLA-B*57:01 presenting N-terminally extended peptides, including the immunodominant HIV-1 Gag epitope TW10 (TSTLQEQIGW), showed that the N terminus protrudes from the peptide-binding groove...
February 20, 2017: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/28197373/systemic-activation-of-antigen-presenting-cells-via-rna-loaded-nanoparticles
#4
Elias J Sayour, Gabriel De Leon, Christina Pham, Adam Grippin, Hanna Kemeny, Joshua Chua, Jianping Huang, John H Sampson, Luis Sanchez-Perez, Catherine Flores, Duane A Mitchell
While RNA-pulsed dendritic cell (DC) vaccines have shown promise, the advancement of cellular therapeutics is fraught with developmental challenges. To circumvent the challenges of cellular immunotherapeutics, we developed clinically translatable nanoliposomes that can be combined with tumor-derived RNA to generate personalized tumor RNA-nanoparticles (NPs) with considerable scale-up capacity. RNA-NPs bypass MHC restriction, are amenable to central distribution, and can provide near immediate immune induction...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28179460/vamp-7-dependent-secretion-at-the-immune-synapse-regulates-antigen-extraction-and-presentation-in-b-lymphocytes
#5
Dorian Obino, Jheimmy Diaz, Juan José Sáez, Jorge Ibañez-Vega, Pablo J Sáez, Martina Alamo, Danielle Lankar, Maria-Isabel Yuseff
Recognition of surface-tethered antigens (Ag) by B cells leads to the formation of an immune synapse that promotes Ag uptake for presentation onto MHC-II molecules. Extraction of immobilized antigens at the immune synapse of B cells relies on the local secretion of lysosomes, which are recruited to the antigen contact site by polarization of their microtubule network. Although conserved polarity proteins have been implicated in coordinating cytoskeleton remodeling with lysosome trafficking, the cellular machinery associated with lysosomal vesicles that regulates their docking and secretion at the synaptic interface has not been defined...
February 8, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28179428/breaking-confinement-unconventional-peptide-presentation-by-major-histocompatibility-mhc-class-i-allele-hla-a-02-01
#6
Soumya G Remesh, Massimo Andreatta, Ge Ying, Thomas Kaever, Morten Nielsen, Curtis McMurtrey, William Hildebrand, Bjoern Peters, Dirk M Zajonc
Peptide antigen-presentation by Major Histocompatibility Class (MHC) I proteins initiates CD8+ T cell mediated immunity against pathogens and cancers. MHC I molecules typically bind peptides with nine amino acids in length with both ends tucked inside the major A and F binding pocket. It has been known for a while that longer peptides can also bind by either bulging out of the groove in the middle of the peptide or by binding in a zig-zag fashion inside the groove. In a recent study, we identified an alternative binding conformation of naturally occurring peptides from Toxoplasma gondii bound by HLA-A*02:01...
February 8, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28168174/sh2-domain-containing-adaptor-protein-b-expressed-in-dendritic-cells-is-involved-in-t-cell-homeostasis-by-regulating-dendritic-cell-mediated-th2-immunity
#7
Md Selim Ahmed, Myeong-Ho Kang, Ezra Lee, Yujin Park, Yideul Jeong, Yong-Soo Bae
PURPOSE: The Src homology 2 domain-containing adaptor protein B (SHB) is widely expressed in immune cells and acts as an important regulator for hematopoietic cell function. SHB silencing induces Th2 immunity in mice. SHB is also involved in T-cell homeostasis in vivo. However, SHB has not yet been studied and addressed in association with dendritic cells (DCs). MATERIALS AND METHODS: The effects of SHB expression on the immunogenicity of DCs were assessed by Shb gene silencing in mouse bone marrow-derived DCs (BMDCs)...
January 2017: Clinical and Experimental Vaccine Research
https://www.readbyqxmd.com/read/28158922/pulmonary-glass-particles-may-persist-in-the-lung-suppressing-function-of-immune-cells
#8
Eun-Jung Park, Gwang-Hee Lee, Jae-Chan Kim, Sang Jin Lee, Kyuhong Lee, Byoung-Seok Lee, Jaerak Chang, Dong-Wan Kim
The health effects of silica may depend on the inherent properties of crystalline silica or on external factors affecting the biological activity or distribution of its polymorphs. Inhaled crystalline silica is classified as a Group I carcinogen, however, information on the health effects of amorphous silica is still insufficient. Considering that alveolar macrophages play a key role in both innate and adaptive immune responses for removal of foreign bodies that enter via the respiratory system, we treated sheet-like glass particles (SGPs), a type of noncrystalline amorphous silica, to MH-S cells, an alveolar macrophage cell line...
February 3, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28154084/lymphocyte-activation-gene-3-a-novel-therapeutic-target-in-chronic-lymphocytic-leukemia
#9
Mika Shapiro, Yair Herishanu, Ben-Zion Katz, Nili Dezorella, Clare Sun, Sigi Kay, Aaron Polliack, Irit Avivi, Adrian Wiestner, Chava Perry
A novel therapeutic approach in cancer, attempting to stimulate host anti-tumor immunity, involves blocking of immune checkpoints. LAG3 is an immune checkpoint receptor expressed on activated/exhausted T-cells. When engaged by MHC class II molecules, LAG3 negatively regulates T-cell function thereby contributing to tumor escape. Intriguingly, a soluble LAG3 variant activates both immune and malignant MHC class II-presenting cells. In this study, we examined the role of LAG3 in the pathogenesis of chronic lymphocytic leukemia, an MHC class II-presenting malignancy, and show that chronic lymphocytic leukemia cells express and secrete LAG3...
February 2, 2017: Haematologica
https://www.readbyqxmd.com/read/28148269/dynadom-structure-based-prediction-of-t-cell-receptor-inter-domain-and-t-cell-receptor-peptide-mhc-class-i-association-angles
#10
Thomas Hoffmann, Antoine Marion, Iris Antes
BACKGROUND: T cell receptor (TCR) molecules are involved in the adaptive immune response as they distinguish between self- and foreign-peptides, presented in major histocompatibility complex molecules (pMHC). Former studies showed that the association angles of the TCR variable domains (Vα/Vβ) can differ significantly and change upon binding to the pMHC complex. These changes can be described as a rotation of the domains around a general Center of Rotation, characterized by the interaction of two highly conserved glutamine residues...
February 2, 2017: BMC Structural Biology
https://www.readbyqxmd.com/read/28141543/molecular-challenges-imposed-by-mhc-i-restricted-long-epitopes-on-t-cell-immunity
#11
Tracy M Josephs, Emma J Grant, Stephanie Gras
It has widely been accepted that major histocompatibility complex class I molecules (MHC-I) are limited to binding small peptides of 8 to 10 residues in length. However, this dogma has recently been challenged with the identification of longer peptides (≥11 residues) that can also elicit cytotoxic CD8+ T cell responses. Indeed, a growing number of studies demonstrate that these non-canonical epitopes are important targets for the immune system. As long epitopes represent up to 10% of the peptide repertoire bound to MHC-I molecules, here we review their impact on antigen presentation by MHC-I, TCR recognition, and T cell immunity...
January 31, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28125356/the-biology-and-underlying-mechanisms-of-cross-presentation-of-exogenous-antigens-on-mhc-i-molecules
#12
Friedrich M Cruz, Jeff D Colbert, Elena Merino, Barry A Kriegsman, Kenneth L Rock
To monitor the health of cells, the immune system tasks antigen-presenting cells with gathering antigens from other cells and bringing them to CD8 T cells in the form of peptides bound to MHC-I molecules. Most cells would be unable to perform this function because they use their MHC-I molecules to exclusively present peptides derived from the cell's own proteins. However, the immune system evolved mechanisms for dendritic cells and some other phagocytes to sample and present antigens from the extracellular milieu on MHC-I through a process called cross-presentation...
January 11, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28119143/grass-carp-ctenopharyngodon-idellus-invariant-chain-of-the-mhc-class-ii-chaperone-protein-associates-with-the-class-i-molecule
#13
Fang-Fang Chen, Hai-Bin Lin, Jin-Chun Li, Yong Wang, Juan Li, Da-Gan Zhang, Wei-Yi Yu
The invariant chain (Ii) is an important immune molecule, as it assists major histocompatibility complex (MHC) class II molecules to present antigenic peptides. The relationship between the Ii and MHC molecules in teleosts remains poorly understood. This study focused on the molecular structure of grass carp Ii (gIi), its organ distribution, correlations with gene transcription, and the association with MHC. gIi cDNA was cloned using designed degenerate primers and the rapid amplification of cDNA ends method (RACE)...
January 21, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28115591/type-ii-nkt-cells-and-their-emerging-role-in-health-and-disease
#14
REVIEW
Madhav V Dhodapkar, Vipin Kumar
NKT cells recognize lipid Ags presented by a class I MHC-like molecule CD1d, a member of the CD1 family. Although most initial studies on NKT cells focused on a subset with semi-invariant TCR termed invariant NKT cells, the majority of CD1d-restricted lipid-reactive human T cells express diverse TCRs and are termed type II NKT cells. These cells constitute a distinct population of circulating and tissue-resident effector T cells with immune-regulatory properties. They react to a growing list of self- as well as non-self-lipid ligands, and share some properties with both invariant NKT and conventional T cells...
February 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28115528/human-dendritic-cell-derived-induced-pluripotent-stem-cell-lines-are-not-immunogenic
#15
Arvind Chhabra, I-Ping Chen, Deepika Batra
Donor-specific induced pluripotent stem cells (iPSC) can be used to generate desired cell types, including naive immune effectors, for the treatment of different diseases. However, a greater understanding of the inherent immunogenicity of human iPSC and their cellular derivatives is needed for the development of safe and effective cell-replacement therapies, given that studies in mouse models claimed that the syngenic mouse iPSC lines can be immunogenic. We report the characterization of the innate and adaptive immune mechanisms in human iPSC lines derived from peripheral blood-derived dendritic cells using a nonintegrating RNA virus, Sendai virus...
January 23, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28115506/characterization-of-t-cells-specific-for-cfp-10-and-esat-6-in-m-tuberculosis-infected-mauritian-cynomolgus-macaques
#16
Amy Ellis, Alexis Balgeman, Mark Rodgers, Cassaundra Updike, Jaime Tomko, Pauline Maiello, Charles A Scanga, Shelby L O'Connor
Nonhuman primates can be used to study host immune responses to Mycobacterium tuberculosis (Mtb). Mauritian cynomolgus macaques (MCMs) are a unique group of animals that have limited MHC genetic diversity, such that MHC-identical animals can be infected with Mtb. Two MCMs homozygous for the relatively common M1 MHC haplotype were bronchoscopically infected with 41 colony-forming units (CFU) Mtb, Erdman strain. Four other MCMs, which had at least one copy of the M1 MHC haplotype, were infected with a lower dose of 3 CFU Mtb...
January 23, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28108559/antigen-processing-in-the-endoplasmic-reticulum-is-monitored-by-semi-invariant-%C3%AE-%C3%AE-tcrs-specific-for-a-conserved-peptide-qa-1-b-mhc-class-ib-ligand
#17
Jian Guan, Soo Jung Yang, Federico Gonzalez, Yuxin Yin, Nilabh Shastri
Ag processing in the endoplasmic reticulum (ER) by the ER aminopeptidase associated with Ag processing (ERAAP) is central to presentation of a normal peptide-MHC class I (MHC I) repertoire. Alternations in ERAAP function cause dramatic changes in the MHC I-presented peptides, which elicit potent immune responses. An unusual subset of CD8(+) T cells monitor normal Ag processing by responding to a highly conserved FL9 peptide that is presented by Qa-1(b), a nonclassical MHC Ib molecule (QFL) in ERAAP-deficient cells...
March 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28094303/genetic-polymorphisms-of-rs3077-and-rs9277535-in-hla-dp-associated-with-systemic-lupus-erythematosus-in-a-chinese-population
#18
Junlong Zhang, Wenli Zhan, Bin Yang, Anning Tian, Lin Chen, Yun Liao, Yongkang Wu, Bei Cai, Lanlan Wang
Although the SLE risk gene loci of HLA-DR and HLA-DQ within the major histocompatibility complex (MHC) region has been gradually revealed by recent Genome-Wide Association studies (GWAS), the association of HLA-DP polymorphisms with SLE was minimally reported. Considering that the variants in rs3077 and rs9277535 in the HLA-DP region could influence the immune response by affecting antigen presentation of HLA class II molecules to CD4(+) T cells, the present study aimed to explore the role of HLA-DP polymorphisms in SLE...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28062921/targeted-deletion-of-traf2-allows-immunosuppression-free-islet-allograft-survival-in-mice
#19
Jeanette E Villanueva, Stacey N Walters, Mitsuru Saito, Elisabeth K Malle, Nathan W Zammit, Katherine A Watson, Robert Brink, Nicole L La Gruta, Stephen I Alexander, Shane T Grey
AIMS/HYPOTHESIS: Administration of anti-CD40 ligand (CD40L) antibodies has been reported to allow long-term islet allograft survival in non-human primates without the need for exogenous immunosuppression. However, the use of anti-CD40L antibodies was associated with thromboembolic complications. Targeting downstream intracellular components shared between CD40 and other TNF family co-stimulatory molecules could bypass these complications. TNF receptor associated factor 2 (TRAF2) integrates multiple TNF receptor family signalling pathways that are critical for T cell activation and may be a central node of alloimmune responses...
January 6, 2017: Diabetologia
https://www.readbyqxmd.com/read/28061947/b-lymphocytes-forming-follicle-like-structures-in-the-lung-tissue-of-tuberculosis-infected-mice-dynamics-phenotypes-and-functional-activity
#20
Irina Linge, Alexander Dyatlov, Elena Kondratieva, Vadim Avdienko, Alexander Apt, Tatiana Kondratieva
During tuberculosis (TB) infection, B cells form follicles in close vicinity of lung granuloma. We assessed the dynamics of follicle formation, surface phenotypes and functional activity of lung B cells during TB course in genetically susceptible mice. The follicles appeared early post infection and peaked at weeks 7-8. Lung B cells resembled classical B2 cells (CD19(+)IgMloIgD(hi)CD1d(-)CD21/35(int)CD5(-)CD11b(-)CD43(-)), but differed from them by the absence of B2 marker CD23. Lung B-cells constitutively expressed MHC II molecules, presented mycobacterial antigens to immune CD4(+) T-cells and produced high amounts of IL-6 and IL-11, but no classical type 1 (TNF-α, IFN-γ), or anti-inflammatory (IL-10, TGF-β) cytokines...
January 2017: Tuberculosis
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