HIV -specific CD8+ T Cell Phenotype and HIV-1 Genetic Diversity PDF Download
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Author: Lyle McKinnon
Publisher:
ISBN:
Category :
Languages : en
Pages : 265
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Author: Lyle McKinnon
Publisher:
ISBN:
Category :
Languages : en
Pages : 265
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Book Description
Author: Kok Keng Tee
Publisher: Frontiers Media SA
ISBN: 2889668991
Category : Science
Languages : en
Pages : 222
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Book Description
Author: R. Ahmed
Publisher: Wiley-Blackwell
ISBN:
Category : Medical
Languages : en
Pages : 754
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Book Description
Persistent Viral Infections Edited by Rafi Ahmed Emory Vaccine Center, Atlanta, USA and Irvin S. Y. Chen UCLA School of Medicine, Los Angeles, USA During the past decade much of our attention has focused on diseases associated with viral persistence. Major breakthroughs in immunology, and the advent of molecular approaches to study pathogenesis have increased our understanding of the complex virus-host interactions that occur during viral persistence. Persistent Viral Infections focuses on: * The pathogenesis and immunology of chronic infections * Animal models that provide, or have the potential to provide, major insights This volume will be essential reading for virologists, immunologists, oncologists and neurologists.
Author: Loury Janbazian
Publisher:
ISBN:
Category :
Languages : en
Pages :
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Author: Melissa Herman
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
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Book Description
For three decades, CD8+ T cells have been implicated in the control of HIV, ever since early studies revealed that a temporal correlation exists between the emergence of CD8+ T cells and the decline of viral loads in HIV infection. Subsequently, a large body of research focusing on the impact of CD8+ T cell responses on HIV has been produced. The central aim of this thesis was to investigate the relationship between CD8+ T cells and control of HIV, with a focus on the differences in CD8+ T cell responses to consensus HIV epitopes and their naturally occurring variants, as well as CD8+ T cell-mediated infection inhibition in disease progression groups. Previous work has indicated that mutations in HIV epitopes of just one or two amino acids can have a drastic impact on the resulting CD8+ T cell response. Considering the extreme genetic diversity of the virus, understanding how CD8+ T cell responses differ to these common natural variants is essential when trying to elucidate what the best targets for an HIV vaccine would be. It was hypothesized that CD8+ T cell responses to consensus HIV epitopes, as a consequence of them being more common in nature, would be more frequent, polyfunctional, and proliferative than responses to their less common variants, as well as being associated with better disease outcomes. After assessing these functional parameters in response to four consensus HIV epitopes and their natural variants, this hypothesis was rejected, and it was determined that the consensus status of an epitope could not reliably dictate the resulting CD8+ T cell response. Rather, it seems more likely that the particular epitope being presented, combined with the HLA allele presenting it and the particular TCRs binding to it, have a much larger impact on the CD8+ T cell response. In the course of this study, the Gag TL9 T variant epitope was identified as stimulating a CD8+ T cell response that is considered to be beneficial in HIV infection. Responses to this epitope were also associated with higher CD4 counts, which, taken together, suggests that this epitope has potential for further research as an HIV vaccine target. In the spectrum of HIV infection, there is a significant amount of heterogeneity in disease progression, whereby some individuals progress to disease more slowly, and others, more rapidly. The mechanisms by which this differential disease progression occurs are not completely understood. It was hypothesized that CD8+ T cells from individuals who progress to disease more slowly (long term non- progressors) would be able to inhibit p24 production in-vitro to a higher degree than CD8+ T cells from individuals who progress more rapidly or at a normal rate (RP/NP). This hypothesis was confirmed, as CD8+ T cells from LTNP individuals were significantly better at inhibiting both secreted and intracellular p24 levels than CD8+ T cells from RP/NPs in an in vitro viral inhibition assay. Overall, these studies confirm that CD8+ T cells are important in control of HIV, as indicated by an increased capacity to inhibit p24 in LTNP individuals. However, it is also clear from this work that the role that CD8+ T cells play in HIV infection is complex, and the responses to HIV epitopes can vary greatly.
Author: Shanthi Ganeshan
Publisher:
ISBN:
Category :
Languages : en
Pages : 484
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Book Description
To explore if genetic diversity was driven by cell-mediated immune responses resulting in adaptive evolution or quasi-neutral mutations, CTL epitope studies were performed. Viral sequences of different HIV-1 genes obtained from two clinical visits from three perinatally infected children were studied. Analyses of these sequences, comprising CTL epitope and nonepitope regions, showed greater genetic variation present for the env and nef genes while the gag and pol genes were relatively conserved. Although the amount of genetic variation in gag, pol and env genes was in agreement with prior studies, the amount of variation observed for nef was greater than previously documented. Analysis of CTL epitope regions showed some epitopes to be extremely conserved, while others had amino acid changes that could possibly produce variants capable of escaping the immune response. Although statistical significance could not be determined, a similar extent of genetic diversity was observed for the epitope and nonepitope regions of a gene, suggesting HIV-1 evolution may not be driven by the CTL response, but rather a process of selection and quasi-neutral mutations. These observations indicate that variation of HIV-1 genes is a result of evolution under the constraints of natural selection imposed by the host.
Author: Pratima Kunwar
Publisher:
ISBN:
Category :
Languages : en
Pages : 133
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Book Description
The enormity of global human immunodeficiency virus type 1 (HIV)/acquired immunodeficiency syndrome (AIDS) pandemic underscores the urgency to develop a safe, effective and accessible prophylactic AIDS vaccine. Multiple lines of evidence in humans and animal models have shown that HIV-1-specific CD8+ cytotoxic T lymphocytes (CTL) are important in controlling and preventing HIV infection. However, the precise qualities of effective epitope-specific CD8+ CTL responses that may be responsible for control remain unclear. Several vaccine strategies have been designed to elicit CD8+ T cell responses against HIV. Previous T cell based vaccine candidates that have failed to offer protection and HIV control primarily induced HIV-1-specific T cells that targeted variable regions of HIV-1. Genetic studies have shown an association between specific human leukocyte antigens (HLAs), (notably HLA-B*27 and -B*57 allele groups) and slower rates of disease progression in the absence of anti-retroviral therapy (ART). HIV-1-specific CD8+ T cells restricted by these HLA alleles are dominant early in infection in individuals expressing these alleles, and predominantly target conserved regions of Gag. These data suggest that an effective T-cell based immunogen should contain conserved regions of HIV-1 as it will increase the likelihood that CD8+ T cells will recognize incoming viral species of diverse clades and decrease the likelihood of rapid escape variants against the recognized epitopes. We extend these observations to comprehensively identify all CD8+ T cell responses that are elicited during early infection. The central goal of this dissertation is to determine if conservation of the epitopes targeted during early HIV-1-infection play an important role on viral control. Here we demonstrate that individuals possessing CD8+ T cells recognizing conserved epitopes of the virus have lower viral load set point than those recognizing only variable epitopes. Collectively, our results imply that the next-generation of T cell based vaccines should focus on strategies that can induce CD8+ T cell responses specifically to conserved regions of HIV-1.
Author: Steven G.E. Marsh
Publisher: Elsevier
ISBN: 0080542506
Category : Medical
Languages : en
Pages : 413
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Book Description
The HLA FactsBook presents up-to-date and comprehensive information on the HLA genes in a manner that is accessible to both beginner and expert alike. The focus of the book is on the polymorphic HLA genes (HLA-A, B, C, DP, DQ, and DR) that are typed for in clinical HLA laboratories. Each gene has a dedicated section in which individual entries describe the structure, functions, and population distribution of groups of related allotypes. Fourteen introductory chapters provide a beginner's guide to the basic structure, function, and genetics of the HLA genes, as well as to the nomenclature and methods used for HLA typing. This book will be an invaluable reference for researchers studying the human immune response, for clinicians and laboratory personnel involved in clinical and forensic HLA typing, and for human geneticists, population biologists, and evolutionary biologists interested in HLA genes as markers of human diversity. Introductory chapters provide good general overview of HLA field for novice immunologists and geneticists Up-to-date, complete listing of HLA alleles Invaluable reference resource for immunologists, geneticists, and cell biologists Combines both structural and functional information, which has never been compiled in a single reference book previously Serological specificity of allotypes Identity of material sequenced including ethnic origin Database accession numbers Population distribution Peptide binding specificities T cell epitopes Amino acid sequences of allotypes Key references
Author: Justine Sunshine
Publisher:
ISBN:
Category :
Languages : en
Pages : 129
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Book Description
Author: Narinder K Mehra
Publisher: Boydell & Brewer Ltd
ISBN: 9788184488708
Category : Medical
Languages : en
Pages : 616
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Book Description
A comprehensive guide to the HLA (Human Leukocyte Antigen) system for immunologists and clinicians, this book contains up-to-date information on the MHC (Major Histocompatibility Complex) and its role in the immune response and in various diseases. The book explores the biological significance and role of the HLA system in organ and haematopoietic stem cell transplantation management. This volume is an invaluable guide to the full spectrum of HLA-related science while also serving as a conceptual and technical resource for those involved in HLA-related research and in clinical or surgical practice. In addition, it will be a primary point of contact for individuals working in other areas who suddenly find that their research is drawing them into the complexities of HLA genetics.
