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Current Opinion in Immunology

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https://www.readbyqxmd.com/read/28538163/metabolic-signatures-of-t-cells-and-macrophages-in-rheumatoid-arthritis
#1
REVIEW
Cornelia M Weyand, Markus Zeisbrich, Jörg J Goronzy
In most autoimmune diseases, a decade-long defect in self-tolerance eventually leads to clinically relevant, tissue-destructive inflammatory disease. The pathogenic potential of chronic persistent immune responses during the pre-clinical and clinical phase is ultimately linked to the bioenergetic fitness of innate and adaptive immune cells. Chronic immune cell stimulation, high cellular turn-over, structural damage to the host tissue and maladaptive wound healing, all require a reliable supply of nutrients, oxygen, and biosynthetic precursors...
May 21, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28535458/mtor-signaling-in-the-differentiation-and-function-of-regulatory-and-effector-t-cells
#2
REVIEW
Hu Zeng, Hongbo Chi
The mechanistic target of rapamycin (mTOR) signaling pathway integrates environmental signals and cellular metabolism to regulate T cell development, activation and differentiation. Recent studies reveal the importance of exquisite control of mTOR activity for proper T cell function, and detailed molecular mechanisms that regulate mTOR signaling in different T cell subsets. Here, we review the latest advances in our understanding of the mTOR pathway and its regulation in the differentiation and function of regulatory T cells and effector T cells...
May 20, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28528220/properties-of-the-tapasin-homologue-tapbpr
#3
REVIEW
Andreas Neerincx, Louise H Boyle
The presentation of antigenic peptides by MHC class I molecules plays a vital role in generating T cell responses against infection and cancer. Over the last two decades the central role of tapasin as a peptide editor that influences the loading and optimisation of peptides onto MHC class I molecules has been extensively characterised. Recently, it has become evident that the tapasin-related protein, TAPBPR, functions as a second peptide editor which influences the peptides displayed by MHC class I molecules...
May 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28528219/the-ongoing-saga-of-the-mechanism-s-of-mhc-class-i-restricted-cross-presentation
#4
Jeff E Grotzke, Debrup Sengupta, Qiao Lu, Peter Cresswell
Cross-presentation is an MHC-I antigen processing pathway that results in the presentation of peptides from exogenous viral, bacterial, parasitic, and tumor antigens and ultimately leads to priming of naïve CD8(+) T cells. This process involves several cellular compartments and multiple components. Successful generation of MHC-I-peptide complexes requires that these components act together in a coordinated fashion. We discuss recent findings on the source of MHC-I, the role of the TAP transporter, the importance of intracellular trafficking events, mechanisms of antigen access the cytosol, and how innate immune signals can affect presentation, with an emphasis on how these pathways compare to conventional antigen presentation and how they correlate with existing data...
May 18, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28521236/targeting-t-cell-metabolism-to-regulate-t-cell-activation-differentiation-and-function-in-disease
#5
REVIEW
Chirag H Patel, Jonathan D Powell
It is becoming increasingly clear that metabolic reprogramming plays a critical role in T cell activation, differentiation and function. To this end, cellular metabolism not only meets the energetic demands of T cells but also provides critical substrates for their growth and function. Furthermore, metabolites themselves are emerging as key regulators of immune responses. As the details of how metabolic reprogramming regulates immune function are revealed, new potential targets for modulating immune responses have emerged...
May 15, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28505602/unusual-antigen-presentation-offers-new-insight-into-hiv-vaccine-design
#6
REVIEW
Andrew J McMichael, Louis J Picker
Recent findings with a rhesus monkey cytomegalovirus based simian immunodeficiency virus vaccine have identified strong CD8+ T cell responses that are restricted by MHC-E. Also mycobacteria specific CD8+ T cells, that are MHC-E restricted, have been identified. MHC-E therefore can present a wide range of epitope peptides to CD8+ T cells, alongside its well defined role in presenting a conserved MHC-class I signal peptide to the NKG2A/C-CD94 receptor on natural killer cells. Here we explore the antigen processing pathways involved in these atypical T cell responses...
May 12, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28494326/mait-cells-and-mr1-antigen-recognition
#7
REVIEW
Andrew N Keller, Alexandra J Corbett, Jacinta M Wubben, James McCluskey, Jamie Rossjohn
Mucosal-associated invariant T cells (MAIT cells) are innate-like T cells that recognise antigens presented by the monomorphic MHC-I related molecule, MR1. Distinct from the conventional MHC-restricted T cell system, MR1 presents small-molecule precursors, derived from microbial biosynthesis of riboflavin, to activate the innate MAIT cell effector potential. Recent data demonstrates how: vitamin B precursors modulate intracellular trafficking of MR1 and impact on MAIT cell development; variation in the MAIT cell antigen receptor sequence impacts MR1-antigen recognition; and most notably, how MR1 can capture chemical identities distinct from riboflavin precursors, including drugs and drug-like molecules...
May 8, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28478383/characterizing-neoantigens-for-personalized-cancer-immunotherapy
#8
REVIEW
Aude-Hélène Capietto, Suchit Jhunjhunwala, Lélia Delamarre
Somatic mutations can generate neoantigens that are presented on MHC molecules and drive effective T cells responses against cancer. Mutation load in cancer patients predicts response to immune checkpoint blockade therapy. Additionally, vaccination targeting neoantigens controls established tumor growth in preclinical models. These recent findings led to a renewed interest in the field of cancer vaccines and the development of antigen-targeted cancer immunotherapies. However, targeting neoantigens is challenging, as most mutations are unique to each cancer patient...
May 4, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28477557/antigen-processing-and-presentation-in-the-thymus-implications-for-t-cell-repertoire-selection
#9
REVIEW
Kenta Kondo, Kensuke Takada, Yousuke Takahama
The processing and presentation of major histocompatibility complex (MHC)-associated antigens depend on the intracellular digestion of self- and nonself-proteins, the loading of digested peptides onto MHC molecules, and the traffic of peptide-MHC complexes to plasma membrane surface for display to interacting T cells. Recent studies have revealed unique machineries for antigen processing and presentation in thymic antigen-presenting cells that display self-antigens to developing thymocytes for the formation of functionally competent yet self-tolerant T cell repertoire...
May 3, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28460345/the-role-of-ampk-in-t-cell-metabolism-and-function
#10
REVIEW
Eric H Ma, Maya C Poffenberger, Alison H-T Wong, Russell G Jones
The AMP-activated protein kinase (AMPK) is a key metabolic regulator that both senses changes in cellular energy levels and activates pathways to maintain cellular energy balance. AMPK achieves this by stimulating catabolic pathways that generate ATP and inhibiting biological pathways that consume ATP consumption. Recent work has established that AMPK is activated in T cells by both immunological and environmental stimuli, and plays an important role in T cell metabolism, in part by controlling T cell 'metabolic plasticity'...
April 28, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28458087/reenergizing-t-cell-anti-tumor-immunity-by-harnessing-immunometabolic-checkpoints-and-machineries
#11
REVIEW
Ping-Chih Ho, Susan M Kaech
T cells patrol our bodies preventing pathogenic infections and malignant cell outgrowth. However, T cells must be properly controlled because aberrant or persistent T cell responses can damage tissues and contribute to autoimmune diseases and other chronic inflammatory diseases including metabolic syndrome. One regulatory mechanism utilized in immune cells is immunometabolic regulation, which ensures immune cells properly respond to systemic and peripheral metabolic cues. Recent work has suggested that deregulated metabolism in tumor cells creates a microenvironmental barrier for mounting effective anti-tumor immune responses...
April 27, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28456018/unique-features-in-the-presentation-of-insulin-epitopes-in-autoimmune-diabetes-an-update
#12
REVIEW
Xiaoxiao Wan, Emil R Unanue
Although an autoimmune disease involves diverse self-antigens, the initiation stage may require recognition of a limited number. This concept is verified in the non-obese diabetic (NOD) mouse model of autoimmune diabetes, in which strong evidence points to insulin as the prime antigen. The NOD mouse bears the I-A(g7) class II-MHC molecules (MHCII) that share common biochemical features and peptidome selection with the human diabetes-susceptible HLA-DQ8. Furthermore, both NOD mice and patients with type 1 diabetes (T1D) display an early appearance of insulin autoantibodies (IAAs) and subsequent insulin-reactive T cell infiltration into the islets...
April 26, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28433952/what-chickens-might-tell-us-about-the-mhc-class-ii-system
#13
REVIEW
Aimée Parker, Jim Kaufman
Almost all knowledge about the structure and function of MHC class II molecules outside of mammals comes from work with chickens. Most of the genes implicated in the class II system are present in chickens, so it is likely that the machinery of antigen processing and peptide-loading is similar to mammals. However, there is only one isotype (lineage) of classical class II genes, with one monomorphic DR-like BLA gene and two polymorphic BLB genes, located near one DMA and two DMB genes. The DMB2 and BLB2 genes are widely expressed at high levels, whereas the DMB1 and BLB1 genes are only expressed at highest levels in spleen and intestine, suggesting the possibility of two class II systems in chickens...
April 20, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28412583/metabolic-reprograming-of-anti-tumor-immunity
#14
REVIEW
Madhusudhanan Sukumar, Rigel J Kishton, Nicholas P Restifo
Immunotherapies designed to trigger T cell destruction of tumor cells can result in sustained and complete responses in patients whose cancers were resistant to available treatment options. Evidence suggests that powering the T cell response - how T cells generate energy - plays an important role in their effectiveness. Furthermore the metabolism of T cells can be modulated to improve their anti-cancer activities. In this review, we will discuss the key metabolic properties of anti-cancer T cells, along with potential strategies to enhance immunotherapy through the modulation of T cell metabolism...
April 13, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28363157/memory-b-cells-total-recall
#15
REVIEW
Tri Giang Phan, Stuart G Tangye
Immunological memory is a cornerstone of adaptive immune responses in higher vertebrates. The remarkable ability to generate memory cells following Ag exposure, in the context of natural infection or immunization, provides long-lived protection against infectious diseases, often for the hosts' lifetime. Indeed, the generation of memory B cells and long-lived plasma cells underpins the success of most vaccines. The concept of immunological memory is not new-it was first proposed nearly 2500 years ago. While our understanding of the complexities of humoral and cell-mediated memory continues to evolve, important aspects of this process remain unresolved...
March 28, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28359987/developmental-options-and-functional-plasticity-of-innate-lymphoid-cells
#16
REVIEW
Ai Ing Lim, Thomas Verrier, Christian Aj Vosshenrich, James P Di Santo
Innate lymphoid cells (ILCs) are lineage- and antigen receptor-negative lymphocytes including natural killer (NK) cells and at least three distinguishable cell subsets (ILC1, ILC2, ILC3) that rapidly produce cytokines (IFN-γ, IL-5, IL-13, IL-17A, IL-22) upon activation. As such, ILCs can act as first-line defenders in the context of infection, inflammation and cancer. Because of the strong conservation between the expression of key transcription factors that can drive signature cytokine outputs in ILCs and differentiated helper T cells, it has been proposed that ILCs represent innate counterparts of the latter...
March 27, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28359914/starving-for-survival-how-catabolic-metabolism-fuels-immune-function
#17
REVIEW
Maria L Balmer, Christoph Hess
Infections disturb homeostasis and often induce a switch to catabolic organismal metabolism. During catabolism, increased systemic availability of glucose, fatty acids and ketone bodies is observed, and recent evidence indicates that these metabolites might serve an immunomodulatory function. However, whereas our understanding of direct pathogen recognition by the host immune system is quite detailed, much less is known about the immunobiology of the metabolic host response to infection. In this review article we briefly discuss how pathogens induce 'dys-homeostasis' systemically, locally, and within cells, and provide examples of how such changes can shape immune-functionality during the course of an infection...
March 27, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28359913/obesity-altered-t-cell-metabolism-and-the-response-to-infection
#18
REVIEW
William D Green, Melinda A Beck
An epidemic of obesity over the past three decades increases the risk of chronic and infectious diseases for adults and children alike. Within the past few years, obesity has been shown to impair the adaptive immune response to infection through alterations in T cell functioning. Growing evidence suggests that perturbations in T cell metabolism drives this stunted immune response, stemming from nutrient, hormone and adipokine dysregulation in the obese. In this review, recent findings in the fields of obesity and T cell mediated immunity demonstrate a unique relationship between altered mechanisms of T cell metabolic homeostasis and plasticity of adaptive immune responses in the obese setting...
March 27, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28359033/regulation-of-memory-b-and-plasma-cell-differentiation
#19
REVIEW
Ryo Shinnakasu, Tomohiro Kurosaki
Memory B cell generation and antibody production result from a differentiation process that begins when the surface BCR on naïve B cells binds an antigen. How the choice between these fates is tempo-spatially regulated is still obscure, but recent advances have reinforced the concept that the combination of B cell-intrinsic heterogeneity and -extrinsic heterogeneity provided by cells such as T cells is a key determinant. As molecular regulators, the transcription factors IRF4 and Bach2, which participate in these fate choices, have been emerging...
March 27, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28355576/role-of-germinal-centers-for-the-induction-of-broadly-reactive-memory-b-cells
#20
REVIEW
Yoshimasa Takahashi, Garnett Kelsoe
Virus-specific memory B cells (Bmem) play a crucial role in protecting against variant viruses. The ability to recognize these variant viruses, defined as antibody breadth, is achieved in Bmem populations by two very different pathways, germline-encoded cross-reactivity and affinity-driven, somatic evolution in germinal centers (GCs) for conserved viral epitopes. The latter class of broadly-reactive Bmem cells are not cross-reactive per se, but bind epitopes crucial for viral fitness. Although these conserved epitopes are often weakly immunogenic, the GC reaction is surprisingly permissive for the continued survival/proliferation of B cells that bind with low affinity or react to cryptic epitopes, increasing their chance of memory recruitment...
March 27, 2017: Current Opinion in Immunology
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