HIV-epitope-specific T cell responses are critical components of the natural immune response to HIV infection, but these cells often become dysfunctional in chronic infection. Structural diversity within the epitope-specific T cell receptor (TCR) repertoire is likely beneficial in the suppression of viral epitope variants. However, the relationship between the structural and clonotypic composition of the HIV-specific TCR repertoire, clonotypic surface and functional phenotype, and avidity for and exposure to antigen is poorly defined. Dominant and sub-dominant epitope-specific T cell clonotypes were identified and the TCR repertoire was assessed over time. Surface expression of PD-1, CD38, CD127, CD45RO, and CCR7 was measured and used to define exhaustion and memory profiles on epitope-specific T cell populations during chronic infection and after initiation of antiretroviral therapy. Dominant clonotypes in chronic infection express a surface phenotype consistent with exhaustion which is ...
BACKGROUNDː The most cause of cancer-related death in women population is breast cancer (BC). Hence, efforts to develop an effective treatment against BC are needed. Since the large proportion of BC is due to over-expression of tumor-associated antigens (TAAs), multi-epitope cancer vaccines are considered as a promising therapeutic approach. The aim of the current study is the production of the novel multi-epitope peptide vaccine against BC in a prokaryotic host. Our novel multi-epitope BC vaccine consists of four sections: 1) cytotoxic T lymphocytes epitopes from human epidermal growth factor receptor, heparanase, mucin 1 protein; 2) helper T lymphocytes epitopes from survivin; 3) a segment of Por B protein a immunostimulatory adjuvant, which was selected from Neisseria meningitides by bioinformatics analysis; 4) a segment of murine ULBP-like transcript 1, which binds to a natural killer group 2 member D receptor in tumor microenvironment with high affinity and stimulates innate immune ...
CD8+ T cells have the potential to control HSV-2 infection. However, limited information has been available on CD8+ T cell epitopes or the functionality of antigen specific T cells during infection or following immunization with experimental vaccines. Peptide panels from HSV-2 proteins ICP27, VP22 and VP13/14 were selected from in silico predictions of binding to human HLA-A*0201 and mouse H-2Kd, Ld and Dd molecules. Nine previously uncharacterized CD8+ T cell epitopes were identified from HSV-2 infected BALB/c mice. HSV-2 specific peptide sequences stabilized HLA-A*02 surface expression with intermediate or high affinity binding. Peptide specific CD8+ human T cell lines from peripheral blood lymphocytes were generated from a HLA-A*02+ donor. High frequencies of peptide specific CD8+ T cell responses were elicited in mice by DNA vaccination with ICP27, VP22 and VP13/14, as demonstrated by CD107a mobilization. Vaccine driven T cell responses displayed a more focused immune response than those induced
Free resource for searching and exporting immune epitopes. Includes more than 95% of all published infectious disease, allergy, autoimmune, and transplant epitope data.
Advances in the field of T cell immunology have contributed to the understanding that cross-reactivity is an intrinsic characteristic of the T cell receptor (TCR), and that each TCR can potentially interact with many different T cell epitopes. To better define the potential for TCR cross-reactivity between epitopes derived from the human genome, the human microbiome, and human pathogens, we developed a new immunoinformatics tool, JanusMatrix, that represents an extension of the validated T cell epitope mapping tool, EpiMatrix. Initial explorations, summarized in this synopsis, have uncovered what appear to be important differences in the TCR cross-reactivity of selected regulatory and effector T cell epitopes with other epitopes in the human genome, human microbiome, and selected human pathogens. In addition to exploring the T cell epitope relationships between human self, commensal and pathogen, JanusMatrix may also be useful to explore some aspects of heterologous immunity and to examine T cell
Jørgensen KW, Rasmussen M, Buus S, Nielsen M. NetMHCstab - predicting stability of peptide:MHC-I complexes; impacts for CTL epitope...
Jørgensen KW, Rasmussen M, Buus S, Nielsen M. NetMHCstab - predicting stability of peptide:MHC-I complexes; impacts for CTL epitope...
The specificity of T cells is determined by the TCR. T cell populations activated and expanded during most in vivo antigen challenges are highly complex, with diverse TCR repertoires, complicating the detection of these cells. The ideal reagent to identify complex epitope-specific T cell populations would be the natural ligand of the TCR, the MHC/epitope complex. However, the affinity of the TCR-MHC/epitope interaction is very low; the association is characterized by a particularly high dissociation rate. To increase the overall avidity of this interaction, MHC/epitope complexes are multimerized into e.g. tetramers. MHC tetramer reagents conjugated with a fluorescent dye can be used in flow cytometry, allowing highly specific detection and isolation of (complex) epitope specific T cell populations directly ex vivo.. The generation of MHC class I multimer reagents has become well established over the past few years. Beta-2-microglobulin and the heavy chains (HC) of MHC molecules are expressed as ...
TCR affinity associated with functional differences between dominant and subdominant SIV epitope-specific CD8+ T cells in Mamu-A*01+ rhesus monkeys.
Free resource for searching and exporting immune epitopes. Includes more than 95% of all published infectious disease, allergy, autoimmune, and transplant epitope data.
Strategy for Identifying Dendritic Cell-Processed CD4 T Cell Epitopes from the HIV Gag p24 Protein. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
ECIA™ Intracellular cytokine staining assay is utilized to detect the antigen-specific T cell responses, immunogenic analysis, epitope discovery at a single cell level for both clinical studies and scientific researches.
We have recently described the first true genome-wide screen for CD4+ T cell reactivity directed against MTB in latent TB infected individuals. The approach relied on predictions of HLA binding capacity for a panel of DR, DP and DQ alleles representative of those most commonly expressed in the general population, coupled with high throughput ELISPOT assays. The results identified hundreds of novel epitopes and antigens, and documented the novel observation that T cells in latent MTB infection are confined to the CXCR3+CCR6+ phenotype and largely directed against three antigenic
EpiToolKit provides a collection of methods from computational immunology for the development of novel epitope-based vaccines including HLA ligand or potential T-Cell epitope prediction, an epitope selection framework for vaccine design, and a method to design optimal string-of-beads vaccines. Additionally, EpiToolKit provides several other tools ranging from HLA typing based on NGS data, to prediction of polymorphic peptides ...
MHC Tetramers for detecting specific T-cell populations. Easy immuophenotyping of your t-cell sample! Class I and II antigen specific tetramers available.
Multiple lines of evidence support a role for CD8(+) T cells in control of acute/early HIV replication; however, features of the primary HIV-specific CD8(+) T cell response that may impact on the efficiency of containment of early viral replication remain poorly defined. In this study, we performed a novel, comprehensive analysis of the kinetics of expansion of components of the HIV-specific CD8(+) T cell response in 21 acutely infected individuals. Epitope-specific T cell responses expanded asynchronously during primary infection in all subjects. The most rapidly expanded responses peaked as early as 5 days following symptomatic presentation and were typically of very limited epitope breadth. Responses of additional specificities expanded and contracted in subsequent waves, resulting in successive shifts in the epitope immunodominance hierarchy over time. Sequence variation and escape were temporally associated with the decline in magnitude of only a subset of T cell responses, suggesting that other
Cytotoxic T lymphocytes (CTLs) play a key role in the control of persistent viral infections. Differences in the quality of this cellular immune response influence the long-term outcome of such infections, but the factors that determine which virus-derived peptide epitopes are targeted by CTLs remain poorly understood. Here, we examine the antigen-processing requirements of three human leukocyte antigen (HLA) A*0201-restricted HIV-1 CTL epitopes. Each of these three peptides appears to be generated by a distinct proteolytic pathway, despite presentation on the cell surface in association with the same HLA class I molecule. Presentation of the commonly immunodominant SLYNTVATL (HIV-1 p17 Gag; residues 77-85) epitope was unaffected by inhibition of the proteasome with lactacystin, but was dependent on the presence of the beta-subunit LMP7. These findings are consistent with emerging data on the complexity of peptide epitope generation, and suggest that differences in antigen processing might contribute to
The chimeric antibodies anti-CD20 rituximab (Rtx) and anti-TNFa infliximab (Ifx) induce antidrug antibodies (ADAs) in many patients with inflammatory diseases. Because of the key role of CD4 T lymphocytes in the initiation of antibody responses, we localized the CD4 T cell epitopes of Rtx and Ifx. With the perspective to anticipate immunogenicity of therapeutic antibodies, identification of the CD4 T cell epitopes was performed using cells collected in healthy donors. Nine T cell epitopes were identified in the variable chains of both antibodies by deriving CD4 T cell lines raised against either Rtx or Ifx. The T cell epitopes often exhibited a good affinity for human leukocyte antigen (HLA)-DR molecules and were part of the peptides identified by MHC-associated peptide proteomics assay from HLA-DR molecules of dendritic cells (DCs) loaded with the antibodies. Two-third of the T cell epitopes identified from the healthy donors stimulated peripheral blood mononuclear cells from patients having ...
The ability of HIV-1-specific CD8(+) T cell responses to recognize epitope variants resulting from viral sequence variation in vivo may affect the ease with which HIV-1 can escape T cell control and impact on the rate of disease progression in HIV-1-infected humans. Here, we studied the functional cross-reactivity of CD8 responses to HIV-1 epitopes restricted by HLA class I alleles associated with differential prognosis of infection. We show that the epitope-specific responses exhibiting the most efficient cross-recognition of amino acid-substituted variants were those strongly associated with delayed progression to disease. Not all epitopes restricted by the same HLA class I allele showed similar variant cross-recognition efficiency, consistent with the hypothesis that the reported associations between particular HLA class I alleles and rate of disease progression may be due to the quality of responses to certain critical epitopes. Irrespective of their efficiency of functional cross-recognition, CD8
The present study focused on three Gag CTL epitopes restricted by three common HLA alleles in Japanese people (24). The Gag protein is most commonly targeted by CTL-inducing HIV/AIDS vaccines (15). In our endogenous expression system, three A*0201-restricted epitope variants and one B*5101-restricted epitope variant escaped from the wild-type CTL recognition, and four A24-restricted epitope variants escaped from the A24-restricted 3R mutant-reactive CTL recognition. Intriguingly, two A*0201-restricted variants and three A24-restricted variants escaped from CTL killing when the gag clones were expressed endogenously in the target cells by the HIV-1 vector, despite the fact that the synthetic variant peptides were well recognized by the CTLs when loaded onto the MHC class I molecule exogenously. The peptide titration experiments have revealed that the strength of these variant peptides recognition was almost equivalent to that of the A*0201-restricted wild-type peptide or the A24-restricted 3R ...
The interaction between a CD4+ TH cell and an antigen presenting cell (APC) is a finely tuned event in adaptive immunity. The affinity is dictated by the T cell receptor (TCR) and the characteristics of antigenic peptide epitopes presented on the major histocompatibility complex class II (pMHC class II) molecules on APCs. Due to the high degree of polymorphism in MHC molecules and the vast repertoire of epitopes that may be presented on each, it is an immense challenge to predict epitopes relevant to disease and homeostasis. It would therefore be of very high value to develop a technology that allows for precise experimental identification of T cell epitopes in the absence of any prior knowledge of the relevant antigen, as long as one has access to T cells. We have developed a novel and generic combinatorial display system for MHC class II, based on phage display. Using phage display, one can probe an epitope sequence space orders of magnitude larger than any cellular or chemical system. As a ...
TY - JOUR. T1 - Refinement in the production and purification of recombinant HCMV IE1-pp65 protein for the generation of epitope-specific T cell immunity. AU - Nguyen, Thi Hoang Oanh. AU - Mifsud, Nicole Andrea. AU - Stewart, Lisbeth A. AU - Rose, Mingus J. AU - Etto, Tamara L. AU - Williamson, Nicholas A. AU - Purcell, Anthony Wayne. AU - Kotsimbos, Tom C. AU - Schwarer, Anthony. PY - 2008. Y1 - 2008. UR - http://www.elsevier.com/locate/yprep. M3 - Article. VL - 61. SP - 22. EP - 30. JO - Protein Expression and Purification. JF - Protein Expression and Purification. SN - 1046-5928. IS - 1. ER - ...
We use cookies to ensure that we give you the best experience on our website. If you click Continue well assume that you are happy to receive all cookies and you wont see this message again. Click Find out more for information on how to change your cookie settings ...
We use cookies to ensure that we give you the best experience on our website. If you click Continue well assume that you are happy to receive all cookies and you wont see this message again. Click Find out more for information on how to change your cookie settings ...
We use cookies to ensure that we give you the best experience on our website. If you click Continue well assume that you are happy to receive all cookies and you wont see this message again. Click Find out more for information on how to change your cookie settings ...
Treatment of invasive adenovirus (Ad) disease in hematopoietic stem cell transplant (SCT) recipients with capsid protein hexon-specific donor T cells is under investigation. We propose that cytotoxic T cells (CTLs) targeted to the late protein hexon may be inefficient in vivo because the early Ad protein E3-19K downregulates HLA class I antigens in infected cells. In this study, CD8+ T cells targeted to highly conserved HLA A2-restricted epitopes from the early regulatory protein DNA polymerase (P-977) and late protein hexon (H-892) were compared in peripheral blood (PB) and tonsils of naturally infected adults. In tonsils, epitope-specific pentamers detected a significantly higher frequency of P-977+CD8+ T cells compared to H-892+CD8+ T cells; this trend was reversed in PB. Tonsil epitope-specific CD8+ T cells expressed IFN-γ and IL-2 but not perforin or TNF-α, whereas PB T cells were positive for IFN-γ, TNF-α, and perforin. Tonsil epitope-specific T cells expressed lymphoid homing marker CCR7 and
Immune monitoring of T cell responses increasingly relies on the use of peptide pools. Peptides, when restricted by the same HLA allele, and presented from within the same peptide pool, can compete for HLA binding sites. What impact such competition has on functional T cell stimulation, however, is not clear. Using a model peptide pool that is comprised of 32 well-defined viral epitopes from Cytomegalovirus, Epstein-Barr virus, and Influenza viruses (CEF peptide pool), we assessed peptide competition in PBMC from 42 human subjects. The magnitude of the peptide pool-elicited CD8 T cell responses was a mean 79% and a median 77% of the sum of the CD8 T cell responses elicited by the individual peptides. Therefore, while the effect of peptide competition was evident, it was of a relatively minor magnitude. By studying the dose-response curves for individual CEF peptides, we show that several of these peptides are present in the CEF-pool at concentrations that are orders of magnitude in excess of what is
Despite progress toward understanding the correlates of protective T cell immunity in HIV infection, the optimal approach to Ag delivery by vaccination remains uncertain. We characterized two immunodominant CD8 T cell populations generated in response to immunization of BALB/c mice with a replication-deficient adenovirus serotype 5 vector expressing the HIV-derived Gag and Pol proteins at equivalent levels. The Gag-AI9/H-2Kd epitope elicited high-avidity CD8 T cell populations with architecturally diverse clonotypic repertoires that displayed potent lytic activity in vivo. In contrast, the Pol-LI9/H-2Dd epitope elicited motif-constrained CD8 T cell repertoires that displayed lower levels of physical avidity and lytic activity despite equivalent measures of overall clonality. Although low-dose vaccination enhanced the functional profiles of both epitope-specific CD8 T cell populations, greater polyfunctionality was apparent within the Pol-LI9/H-2Dd specificity. Higher proportions of central ...
Fingerprint Dive into the research topics of Recognition of naturally processed and ovarian cancer reactive CD8 ,sup,+,/sup, T cell epitopes within a promiscuous HLA class II T-helper region of NY-ESO-1. Together they form a unique fingerprint. ...
easYmer HLA-B*46:01 MHC Tetramers Kit can be used to generate monomers with your choice of peptide and to analyze T-cells by flow cytometry.
A method for updating detecting and loading CD volume indexes from a multiple-CD set to a cumulative volume table contained in a computer memory. The method employs an volume index file on each intermediate CD of the set along with a dual index file feature on the last CD of the set. The second index file on the last CD is a cumulative file of all the index files contained on all the CDs of the set. The cumulative index file on the last CD is compared to the cumulative volume table to generate a list of missing volumes which have not already been loaded into computer memory. The method permits determining whether a given CD is a single CD or a CD that is one of a multiple-CD set by detecting the presence of a second volume index file on the CD.
p286/I-Ag7 tetramer-positive CD4+ T cells from G286 mice delay diabetes transfer. Tetramer-positive and -negative cells were sorted from G286 lymph node cells w
Moradian N, Ochs HD, Sedikies C, Hamblin MR, Camargo CA Jr, Martinez JA, Biamonte JD, Abdollahi M, Torres PJ, Nieto JJ, Ogino S, Seymour JF, Abraham A, Cauda V, Gupta S, Ramakrishna S, Sellke FW, Sorooshian A, Wallace Hayes A, Martinez-Urbistondo M, Gupta M, Azadbakht L, Esmaillzadeh A, Kelishadi R, Esteghamati A, Emam-Djomeh Z, Majdzadeh R, Palit P, Badali H, Rao I, Saboury AA, Jagan Mohan Rao L, Ahmadieh H, Montazeri A, Fadini GP, Pauly D, Thomas S, Moosavi-Movahed AA, Aghamohammadi A, Behmanesh M, Rahimi-Movaghar V, Ghavami S, Mehran R, Uddin LQ, Von Herrath M, Mobasher B, Rezaei N. ...
Dear Netters, Does anyone know of any software for the prediction of T-cell epitopes from peptide sequences? I have access to Mac, PC, VAX, SG & UNIX so the program format does not matter. Hope to hear from someone soon! Thanks, Brian Robertson Max-Planck-Institut fuer Biologie Abt. Infektionsbiologie D74 Tuebingen, FRG. Email robertson at mpib-tuebingen.mpg.de ...
We use cookies to ensure that we give you the best experience on our website. If you click Continue well assume that you are happy to receive all cookies and you wont see this message again. Click Find out more for information on how to change your cookie settings ...
CTL recognition and antagonism by naturally occurring p17 variants. Recognition of variant peptides by two donor 008 clones (18 and 20) (a and b) at an ET of 8
This study demonstrates that use of structural information improves the definition and optimization of cytotoxic T lymphocyte (CTL) epitopes. Epitope optimization usually requires numerous truncated peptides or a reverse immunogenetic approach, where the peptide binding motif is used to predict epitopes. These binding motifs do not reliably predict all peptides which are CTL epitopes. Comparison of 24 peptides eluted from HLA-B8 with 10 HLA-B8-restricted defined CTL epitopes demonstrated that known epitopes varied considerably at anchor positions. We used structural information based on determination of the crystal structure of the HLA-B8-GGKKKYKL complex to reassess previously described CTL epitopes, to predict new epitopes, and to predict the consequences of naturally occurring variation within epitopes. These predictions were confirmed by cytotoxicity and binding assays. Use of combined structural and immunological data more accurately defines the true peptide-binding motif of a restriction element
Virus-specific cytotoxic T-lymphocyte (CTL) responses are critical in the control of human immunodeficiency virus type 1 (HIV-1) infection and will play an important part in therapeutic and prophylactic HIV-1 vaccines. The identification of virus-specific epitopes that are efficiently recognized by CTL is the first step in the development of future vaccines. Here we describe the immunological characterization of a number of novel HIV-1-specific, HLA-A2-restricted CTL epitopes that share a high degree of conservation within HIV-1 and a strong binding to different alleles of the HLA-A2 superfamily. These novel epitopes include the first reported CTL epitope in the Vpr protein. Two of the novel epitopes were immunodominant among the HLA-A2-restricted CTL responses of individuals with acute and chronic HIV-1 infection. The novel CTL epitopes identified here should be included in future vaccines designed to induce HIV-1-specific CTL responses restricted by the HLA-A2 superfamily and will be important to
PubMed journal article Identification and characterization of a human agonist cytotoxic T-lymphocyte epitope of human prostate-specific antige were found in PRIME PubMed. Download Prime PubMed App to iPhone, iPad, or Android
We use cookies to ensure that we give you the best experience on our website. If you click Continue well assume that you are happy to receive all cookies and you wont see this message again. Click Find out more for information on how to change your cookie settings ...
In the course of constructing a recombinant vaccinia virus encoding the influenza A nucleoprotein (NP) gene preceded by the hemagglutinin leader sequence, we isolated a single base-pair deletion mutant which gave rise to L+NP(1-159) in which only the first 159 amino acids were in frame. Despite this, when we infected target cells, we found that the point mutant was able to sensitize them for lysis not only by cytotoxic T cells recognizing residues 50-58 (the in-frame portion), but also by CTL to epitopes which are downstream of the mutation (366-374 and 378-386). Furthermore, normal C57BL/6 mice can be primed with the frameshift NP to recognize the immunodominant Db-restricted epitope 366-374 (which is out of frame). Experiments in which the mutant gene product was processed in the endoplasmic reticulum of target cells suggested that the apparent suppression occurred during polypeptide extension.
In the course of constructing a recombinant vaccinia virus encoding the influenza A nucleoprotein (NP) gene preceded by the hemagglutinin leader sequence, we isolated a single base-pair deletion mutant which gave rise to L+NP(1-159) in which only the first 159 amino acids were in frame. Despite this, when we infected target cells, we found that the point mutant was able to sensitize them for lysis not only by cytotoxic T cells recognizing residues 50-58 (the in-frame portion), but also by CTL to epitopes which are downstream of the mutation (366-374 and 378-386). Furthermore, normal C57BL/6 mice can be primed with the frameshift NP to recognize the immunodominant Db-restricted epitope 366-374 (which is out of frame). Experiments in which the mutant gene product was processed in the endoplasmic reticulum of target cells suggested that the apparent suppression occurred during polypeptide extension.
We use cookies to ensure that we give you the best experience on our website. If you click Continue well assume that you are happy to receive all cookies and you wont see this message again. Click Find out more for information on how to change your cookie settings ...
The proteasome, an essential component of the ATP-dependent proteolytic pathway in eukaryotic cells, is responsible for the degradation of most cellular proteins and is believed to be the main source of MHC class I-restricted antigenic peptides for presentation to CTL. Inhibition of the proteasome by lactacystin or various peptide aldehydes can result in defective Ag presentation, and the pivotal role of the proteasome in Ag processing has become generally accepted. However, recent reports have challenged this observation. Here we examine the processing requirements of two HLA A*0201-restricted epitopes from HIV-1 reverse transcriptase and find that they are produced by different degradation pathways. Presentation of the C-terminal ILKEPVHGV epitope is impaired in ME275 melanoma cells by treatment with lactacystin, and is independent of expression of the IFN-gamma-inducible proteasome beta subunits LMP2 and LMP7. In contrast, both lactacystin treatment and expression of LMP7 induce the presentation of
The identification of class II binding peptide epitopes from autoimmune disease-related antigens is an essential step in the development of antigen-specific immune modulation therapy. In the case of type 1 diabetes, T cell and B cell reactivity to the autoantigen glutamic acid decarboxylase 65 (GAD65) is associated with disease development in humans and in nonobese diabetic (NOD) mice. In this study, we identify two DRB1*0401-restricted T cell epitopes from human GAD65, 274-286, and 115-127. Both peptides are immunogenic in transgenic mice expressing functional DRB1*0401 MHC class II molecules but not in nontransgenic littermates. Processing of GAD65 by antigen presenting cells (APC) resulted in the formation of DRB1*0401 complexes loaded with either the 274-286 or 115-127 epitopes, suggesting that these naturally derived epitopes may be displayed on APC recruited into pancreatic islets. The presentation of these two T cell epitopes in the islets of DRB1*0401 individuals who are at risk for type 1
Vaccines designed to stimulate CTL should be able to deliver protein antigens to the cytoplasm of host cells for processing and presentation by MHC-I. Many systems have been exploited to accomplish cytoplasmic delivery, including viral and bacterial vectors and DNA vaccines (7, 8, 14, 22, 27, 33, 36). There have also been reports demonstrating that antiviral immunity can be primed in mice vaccinated with a recombinant Bordetella adenylate cyclase toxin incorporating a CTL epitope from LCMV (11, 29, 31); however, the data demonstrated protection only when the recombinant toxin was injected in the presence of an adjuvant, aluminum hydroxide (29). Therefore, it remains unclear whether the antiviral protection was a result of toxin delivery or adjuvant activity. This report describes the use of a nontoxic, truncated form of anthrax toxin as an epitope delivery system without the use of adjuvant.. We demonstrate that protective immunity against a viral pathogen, LCMV, is generated in BALB/c mice ...
MHC-binding predictions have facilitated T cell epitope discovery by narrowing the search space to a manageable number of likely peptide candidates. Compared with approaches that do not use predictions, such as screening overlapping peptides, a downside of the prediction approach was that peptides of noncanonical lengths were missed (35). Naively, one could simply extend binding predictions to peptides of any length and rank all peptides based on their predicted affinity. But, as demonstrated in our study, although peptides of noncanonical lengths might have similar or even better predicted binding affinities than the canonical 9mer peptides, they end up being underrepresented among the naturally presented ligands eluted from MHC molecules and, consequently, are recognized less frequently by T cells. In this study, we explained these similarities between the length profiles of naturally presented peptides by fitting a common, underlying peptide-length distribution. This common length ...
The precise role played by HIV-specific cytotoxic T lymphocytes (CTL) in HIV infection remains controversial. Despite strong CTL responses being generated during the asymptomatic phase, the virus persists and AIDS ultimately develops. It has been argued that the virus is so variable, and the virus turnover so great that escape from CTL recognition would occur continually, but so far there is limited evidence for CTL escape. The opposing argument is that evidence for CTL escape is present but hard to find because multiple anti-HIV immune responses are acting simultaneously during the asymptomatic phase of infection. We describe six donors who make a strong CTL response to an immunodominant HLA-B27-restricted epitope. In the two donors who progressed to AIDS, CTL escape to fixation by the same mutation was observed, but only after 9-12 years of epitope stability. CTL escape may play an important role in the pathogenesis of HIV infection.
We use cookies to ensure that we give you the best experience on our website. If you click Continue well assume that you are happy to receive all cookies and you wont see this message again. Click Find out more for information on how to change your cookie settings ...
In this study we show that the HPV16 E7-specific CD8+ T cell response is far more vigorous after vaccination with a HPV16 E7-derived 35-residue long peptide than following vaccination with the minimal CTL epitope. Our data suggest that two distinct DC-related mechanisms lie at the basis of this result. First, the long peptide contains both a CTL epitope and a Th epitope. Prime-boost vaccinations of wild-type, MHC class II−/−, and CD40−/− mice show that the CD40-CD40L interactions between APC and E7-specific Th cells contribute considerably to the level of the CD8+ T cell response. Second, under circumstances excluding T cell help, a comparison of the CD8+ T cell responses induced by either the minimal CTL epitope (nine residues) or the long peptide combined with DC-activating agents demonstrates that vaccination with the long peptide results in far better responses. This suggests that compared with the short minimal CTL epitope the long peptide is much better presented by professional ...
A long-standing question in the field of immunology concerns the factors that contribute to Th cell epitope immunodominance. For a number of viral membrane proteins, Th cell epitopes are localized to exposed protein surfaces, often overlapping with Ab binding sites. It has therefore been proposed that Abs on B cell surfaces selectively bind and protect exposed protein fragments during Ag processing, and that this interaction helps to shape the Th cell repertoire. While attractive in concept, this hypothesis has not been thoroughly tested. To test this hypothesis, we have compared Th cell peptide immunodominance in normal C57BL/6 mice with that in C57BL/6( micro MT/ micro MT) mice (lacking normal B cell activity). Animals were first vaccinated with DNA constructs expressing one of three different HIV envelope proteins, after which the CD4(+) T cell response profiles were characterized toward overlapping peptides using an IFN-gamma ELISPOT assay. We found a striking similarity between the peptide ...
We recently discover a new immune escape mechanism that may help viruses escape from immune detection, which might compromise vaccine efficacy. Viruses that cause chronic infection in human contain higher numbers of T cell epitopes whose TCR-facing amino acids are identical to those of numerous peptides from the human proteome. We postulate that viruses that incorporate such human-like epitopes may exploit host tolerance to avoid or suppress effector responses. In order to predict these human-like epitopes, we developed an immunoinformatics tool, JanusMatrix.. Using JanusMatrix, we have identified T cell epitopes in H7N9 influenza HA protein that are highly conserved with human genome epitopes, and these epitopes possess low immunogenicity, activate natural Tregs and suppress bystander effector T cell responses in vitro. The human like T cell epitopes may contribute to the delayed, low titer of H7N9 hemagglutination inhibiting antibody responses and diminished seroconversion rates that have been ...
This graph shows the total number of publications written about Immunodominant Epitopes by people in this website by year, and whether Immunodominant Epitopes was a major or minor topic of these publications ...
The Experimental Analysis of Mutlitple Computationally-Driven Methods for the Deletion of Broadly Distributed T cell Epitopes in a Functional Biotherapeutic Candidate A Thesis Submitted to the Faculty in partial fulfillm ent o f the requirements for the degree of D octor o f Philosophy by Regina Salvat Thayer School o f Engineering D artmouth College Hanover, N ew Hampshire January 4, 2015 Chairman Exam ining Committee: Professor Karl Griswold M em ber Professor M argaret Ackerman M em ber Professor Chris Bailey-Kellogg M emb er___________________________ Professor Lenny M oise F. Jon Kull Dean o f Graduate Studies ...
A free platform for explaining your research in plain language, and managing how you communicate around it - so you can understand how best to increase its impact.
Fingerprint Dive into the research topics of TAP-independent presentation of CTL epitopes by Trojan antigens. Together they form a unique fingerprint. ...
Peptide tools for target & epitope discovery, development of treatment & diagnosis of allergies, such as food allergy, atopic dermatitis, allergic asthma…
Rational design of immunotherapeutics relies on clear knowledge of the immunodominant epitopes of antigens. Current methods for identifying kinetically stable peptide-MHC complexes are in many cases i
Peptides that combine poorly to MHC course We substances elicit low functional avidity Capital t cell reactions often. immune system reactions can become increased towards Capital t cell epitopes with low practical avidity by raising antigen denseness. We also determined a heteroclitic epitope (RCVIFANI) that elicited a Capital t cell response with almost full cross-reactivity with indigenous epitope and proven improved MHC-peptide plethora likened to indigenous S i9000598. Structural and thermal dissolve studies indicated that the Queen600V replacement improved balance of the peptide-MHC complicated without significantly changing the antigenic surface area, causing in cross-reactive Big t cell reactions extremely. Our data high light that improved pMHC Rabbit polyclonal to IL25 complicated screen contributes to heteroclitic epitope effectiveness and explain guidelines for increasing immune system reactions that cross-react with the indigenous epitope. Intro growth and Virus distance both ...
T cells play pivotal roles in shaping host immune responses in infectious diseases, autoimmunity and cancer. The activation of T cells requires immune and growth factor-derived signals. However, alterations in nutrients and metabolic signals tune T cell responses by impinging upon T cell fates and immune functions. In this review, we summarize how key nutrients, including glucose, amino acids and lipids, and their sensors and transporters shape T cell responses. We also briefly discuss regulation of T cell responses by oxygen and energy sensing mechanisms.
Analysis of cytotoxic T cell epitopes in relation to cancer. / Stranzl, Thomas; Brunak, Søren (Main supervisor); Larsen, Mette Voldby (Supervisor).. Kgs. Lyngby : Technical University of Denmark (DTU), 2012. 97 p.. Publication: Research › Ph.D. thesis - Annual report year: 2012 ...
In this study we characterized the CTL response induced in vivo against TS/A mouse adenocarcinoma cells genetically engineered to express different cytokine or costimulatory molecules, i.e., IFN-α, IFN-γ, IL-4, and B7.1. Independent of the molecule introduced, the CTL response elicited was constantly directed against a single immunodominant epitope represented by the AH1 peptide derived from the gp70 product of an endogenous MuLV and corresponding to amino acids 423-431 of the protein (19) . Indeed, tumor rejection was accompanied by increases in a CD8+ T-cell population that was stainable with gp70-specific tetramers; moreover, independent in vitro restimulation of splenocytes from mice that had rejected a primary TS/A tumor challenge with either gp70423-431 peptide or engineered TS/A, which provided the entire antigenic array of the tumor cells, produced a similar large increase in CTLs specifically recognizing the AH1 antigenic epitope. Finally, MLTC lytic activity could be inhibited in an ...
Authors: AI Webb, MA Dunstone, WS Chen, MI Aguilar, QY Chen, H Jackson, L Chang, L Kjer-Nielsen, T Beddoe, J McCluskey, J Rossjohn, AW Purcell