共查询到20条相似文献,搜索用时 0 毫秒
1.
Uthaman Gowthaman Sathi Babu Chodisetti Pankaj Parihar Javed N. Agrewala 《Amino acids》2010,38(5):1333-1342
Since CD8+ T cell response is crucial to combat intracellular infections and cancer, identification of class I HLA binding peptides
is of immense clinical value. The experimental identification of such peptides is protracted and laborious. Exploiting in
silico tools to discover such peptides is an attractive alternative. However, this approach needs a thorough assessment before
its elaborate application. We have adopted a reverse approach to evaluate the reliability of eight different servers (inclusive
of 55 predictors) by exploiting experimentally proven data. A comprehensive data set of more than 960 peptides was employed
to test the efficacy of the programs. We have validated commonly used strategies to predict peptides that bind to seven most
prevalent HLA class I alleles. We conclude that four of the eight servers are more adept in predictions. Although the overall
predictions for class I MHC binders were superior to class II MHC binders, individual predictors for different alleles belonging
to the same program were highly variable in their efficiencies. We have also addressed whether a consensus approach can yield
better prediction efficiency. We observed that combining the results from different in silico programs could not increase
the efficiency significantly. 相似文献
2.
Christian Paul Johannes P. Haas Ulrich Schoenwald Hans Truckenbrodt Maria P. Bettinotti Jürgen Bönisch Günter Brünnler Elisabeth Keller Claudia Nevinny-Stickel Zhu Yao Ekkehard D. Albert 《Immunogenetics》1994,39(1):61-64
The data presented here are part of the doctoral thesis of C. Paul. 相似文献
3.
Investigation of peptide involvement in T cell allorecognition using recombinant HLA class I multimers 总被引:2,自引:0,他引:2
Whitelegg AM Oosten LE Jordan S Kester M van Halteren AG Madrigal JA Goulmy E Barber LD 《Journal of immunology (Baltimore, Md. : 1950)》2005,175(3):1706-1714
Alloreactive T cells are involved in injurious graft rejection and graft-vs-host disease. However, they can also evoke beneficial responses to tumor Ags restricted by foreign MHC molecules. Manipulation of these alloreactivities requires information on the basis of T cell allorecognition. The vigorous T cell response to foreign MHC molecules may arise from peptide-independent recognition of polymorphic residues of foreign MHC molecules or peptide-specific recognition of novel peptides presented by foreign MHC molecules. We investigated CD8+ T cell allorecognition using recombinant HLA class I/peptide complexes. Peptide-specific allorecognition was examined using tetramers of HLA-A*0201 representing five peptides derived from ubiquitously expressed self-proteins that are known to bind endogenously to HLA-A*0201. Distinct subsets of CD8+ T cells specific for each HLA-A*0201/peptide combination were detected within four in vitro-stimulated T cell populations specific for foreign HLA-A*0201. Peptide-independent allorecognition was investigated using artificial Ag-presenting constructs (aAPCs) coated with CD54, CD80, and functional densities of a single HLA-A*0201/peptide combination for four different peptides. None of the four T cell populations specific for foreign HLA-A*0201 were stimulated by the aAPCs, whereas they did produce IFN-gamma upon stimulation with cells naturally expressing HLA-A*0201. Thus, aAPCs did not stimulate putative peptide-independent allorestricted T cells. The results show that these alloreactive populations comprise subsets of T cells, each specific for a self-peptide presented by foreign class I molecules, with no evidence of peptide-independent components. 相似文献
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5.
Zhang CC Rogalski JC Evans DM Klockenbusch C Beavis RC Kast J 《Journal of proteome research》2011,10(2):656-668
Experiments to probe for protein-protein interactions are the focus of functional proteomic studies, thus proteomic data repositories are increasingly likely to contain a large cross-section of such information. Here, we use the Global Proteome Machine database (GPMDB), which is the largest curated and publicly available proteomic data repository derived from tandem mass spectrometry, to develop an in silico protein interaction analysis tool. Using a human histone protein for method development, we positively identified an interaction partner from each histone protein family that forms the histone octameric complex. Moreover, this method, applied to the α subunits of the human proteasome, identified all of the subunits in the 20S core particle. Furthermore, we applied this approach to human integrin αIIb and integrin β3, a major receptor involved in the activation of platelets. We identified 28 proteins, including a protein network for integrin and platelet activation. In addition, proteins interacting with integrin β1 obtained using this method were validated by comparing them to those identified in a formaldehyde-supported coimmunoprecipitation experiment, protein-protein interaction databases and the literature. Our results demonstrate that in silico protein interaction analysis is a novel tool for identifying known/candidate protein-protein interactions and proteins with shared functions in a protein network. 相似文献
6.
Tumor membrane Ag immobilized on cell size microspheres (large multivalent immunogen (LMI)) was previously shown to augment tumor-specific CTL activity and reduce tumor growth, and a clinical trial examining this approach is in progress. In the current study, LMI treatment has been examined using adoptive transfer of TCR-transgenic CD8 T cells to visualize Ag-specific cells during the response. OT-I T cells specific for H-2K(b)/OVA(257-264) were transferred into mice that were then challenged with LMI made by immobilizing H-2K(b)/OVA(257-264) on microspheres (K(b)/OVA(257-264)-LMI) alone, or along with i.p. challenge with OVA-expressing E.G7 tumor. K(b)/OVA(257-264)-LMI caused significant reduction of tumor growth when administered to E.G7-bearing mice. When administered alone, the K(b)/OVA(257-264)-LMI caused only weak clonal expansion of OT-I cells in the spleen and lymph nodes, although most of the OT-I cells up-regulated expression of CD44 and VLA-4. In contrast, K(b)/OVA(257-264)-LMI administration to E.G7-bearing mice stimulated no detectable expansion of OT-I cells in the spleen and lymph nodes but caused a rapid increase in the number of OT-I cells in the peritoneal cavity, the site of the growing tumor. These results demonstrate the potential for using class I/tumor peptide complexes for immunotherapy. In addition, they suggest a model for the mechanism of CTL augmentation in which recognition of the LMI Ag results in altered trafficking of the tumor-specific CD8 T cells so that they reach the site of a growing tumor more rapidly and in greater numbers, where they may further expand and acquire effector function. 相似文献
7.
Marvin M. van Luijn Martine E. D. Chamuleau Maaike E. Ressing Emmanuel J. Wiertz Suzanne Ostrand-Rosenberg Yuri Souwer Adri Zevenbergen Gert J. Ossenkoppele Arjan A. van de Loosdrecht S. Marieke van Ham 《Cancer immunology, immunotherapy : CII》2010,59(12):1825-1838
During HLA class II synthesis in antigen-presenting cells, the invariant chain (Ii) not only stabilizes HLA class II complexes
in the endoplasmic reticulum, but also mediates their transport to specialized lysosomal antigen-loading compartments termed
MIICs. This study explores an alternative HLA class II presentation pathway in leukemic blasts that involves proteasome and
transporter associated with antigen processing (TAP)-dependent peptide loading. Although HLA-DR did associate with Ii, Ii
silencing in the human class II-associated invariant chain peptide (CLIP)-negative KG-1 myeloid leukemic cell line did not
affect total and plasma membrane expression levels of HLA-DR, as determined by western blotting and flow cytometry. Since
HLA-DR expression does require peptide binding, we examined the role of endogenous antigen-processing machinery in HLA-DR
presentation by CLIP− leukemic blasts. The suppression of proteasome and TAP function using various inhibitors resulted in decreased HLA-DR levels
in both CLIP− KG-1 and ME-1 blasts. Simultaneous inhibition of TAP and Ii completely down-modulated the expression of HLA-DR, demonstrating
that together these molecules form the key mediators of HLA class II antigen presentation in leukemic blasts. By the use of
a proteasome- and TAP-dependent pathway for HLA class II antigen presentation, CLIP− leukemic blasts might be able to present a broad range of endogenous leukemia-associated peptides via HLA class II to activate
leukemia-specific CD4+ T cells. 相似文献
8.
Kambayashi T Kraft-Leavy JR Dauner JG Sullivan BA Laur O Jensen PE 《Journal of immunology (Baltimore, Md. : 1950)》2004,172(3):1661-1669
The MHC class Ib molecule Qa-1 is the primary ligand for mouse CD94/NKG2A inhibitory receptors expressed on NK cells, in addition to presenting Ags to a subpopulation of T cells. CD94/NKG2A receptors specifically recognize Qa-1 bound to the MHC class Ia leader sequence-derived peptide Qdm. Qdm is the dominant peptide loaded onto Qa-1 under physiological conditions and this peptide has an optimal sequence for binding to Qa-1. Peptide dissociation experiments demonstrated that Qdm dissociates from soluble or cell surface Qa-1(b) molecules with a t(1/2) of approximately 1.5 h at 37 degrees C. In comparison, complexes of an optimal peptide (SIINFEKL) bound to the MHC class Ia molecule H-2K(b) dissociated with a t(1/2) in the range from 11 to 31 h. In contrast to K(b), the stability of cell surface Qa-1(b) molecules was independent of bound peptides, and several observations suggested that empty cell surface Qa-1(b) molecules might be unusually stable. Consistent with the rapid dissociation rate of Qdm from Qa-1(b), cells become susceptible to lysis by CD94/NKG2A(+) NK cells under conditions in which new Qa-1(b)/Qdm complexes cannot be continuously generated at the cell surface. These results support the hypothesis that Qa-1 has been selected as a specialized MHC molecule that is unable to form highly stable peptide complexes. We propose that the CD94/NKG2A-Qa-1/Qdm recognition system has evolved as a rapid sensor of the integrity of the MHC class I biosynthesis and Ag presentation pathway. 相似文献
9.
Navya?Raj Agnes?Helen N.?Manoj G.?Harish Vipin?Thomas Shailja?Singh Seema?Sehrawat Shaguna?Seth Achuthsankar?S.?Nair Abhinav?Grover Pawan?K.?Dhar
Peptides are increasingly used as inhibitors of various disease specific targets. Several naturally occurring and synthetically developed peptides are undergoing clinical trials. Our work explores the possibility of reusing the non-expressing DNA sequences to predict potential drug-target specific peptides. Recently, we experimentally demonstrated the artificial synthesis of novel proteins from non-coding regions of Escherichia coli genome. In this study, a library of synthetic peptides (Synpeps) was constructed from 2500 intergenic E. coli sequences and screened against Beta-secretase 1 protein, a known drug target for Alzheimer’s disease (AD). Secondary and tertiary protein structure predictions followed by protein–protein docking studies were performed to identify the most promising enzyme inhibitors. Interacting residues and favorable binding poses of lead peptide inhibitors were studied. Though initial results are encouraging, experimental validation is required in future to develop efficient target specific inhibitors against AD. 相似文献
10.
Thomson CT Kalergis AM Sacchettini JC Nathenson SG 《Journal of immunology (Baltimore, Md. : 1950)》2001,166(6):3994-3997
The vesicular stomatitis virus (VSV) octapeptide RGYVYQGL binds to H-2K(b) and triggers a cytotoxic T cell response in mice. A variant peptide, RGYVYEGL (E6) with a glutamic acid for glutamine replacement at position 6 of the VSV peptide, elicits a T cell response with features that are quite different from those elicited by the wild-type VSV peptide. The differences found in the nature of the T cells responding to the E6 peptide include changes in both the V beta elements and the sequences of the complementarity-determining region 3 loops of their TCRs. Further experiments found that the E6 peptide can act as an antagonist for VSV-specific T cell hybridomas. To determine whether these differences in V beta usage, complementarity-determining region 3 sequences, and the switch from agonism to antagonism are caused by a conformational change on the MHC, the peptide, or both, we determined the crystal structure of the variant E6 peptide bound to H-2K(b). This structure shows that the only significant structural difference between H-2K(b)/E6 and the previously determined H-2K(b)/VSV is limited to the side chain of position 6 of the peptide, with no differences in the MHC molecule. Thus, a minor conformational change in the peptide can profoundly alter the biological outcome of the TCR-peptide/MHC interaction. 相似文献
11.
To generate an effective immune response, class II major histocompatibility complex molecules (MHCII) must present a diverse array of peptide ligands for recognition by T lymphocytes. Peptide/MHCII complexes are stabilized by hydrophobic anchoring of peptide side chains to pockets in the MHCII protein and the formation of hydrogen bonds to the peptide backbone. Many current models of peptide/MHCII association assume an additive and independent contribution of the interactions between major MHCII pockets and corresponding side chains in the peptide. However, significant conformational rearrangements occur in both the peptide and MHCII during binding. Therefore, we hypothesize that peptide binding to MHCII could be viewed as a folding process in which both molecules cooperate to produce the final conformation. To directly test this hypothesis, we adapt a serial mutagenesis strategy to study cooperativity in the interaction of the human MHCII HLA-DR1 and a peptide derived from influenza hemagglutinin. Substitutions in either the peptide or HLA-DR1 that are predicted to interfere with hydrogen bond formation show cooperative effects on complex stability and affinity. Substitution of a peptide side chain that provides a hydrophobic contact also contributes to the cooperative effect, suggesting a role for all energetic sources in the folding process. We propose that cooperativity throughout the peptide-binding groove reflects the folding of segments of the MHCII molecule into helices around the peptide with a concomitant folding of the peptide into a polyproline helix. The implications of cooperativity for peptide/MHCII structure and epitope selection are discussed. 相似文献
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13.
An efficient and versatile mammalian viral vector system for major histocompatibility complex class I/peptide complexes 下载免费PDF全文
Kawana-Tachikawa A Tomizawa M Nunoya J Shioda T Kato A Nakayama EE Nakamura T Nagai Y Iwamoto A 《Journal of virology》2002,76(23):11982-11988
We report a Sendai virus (SeV) vector system for expression of major histocompatibility complex (MHC) class I/peptide complexes. We cloned the extracellular domain of a human MHC class I heavy chain, HLA-A*2402, and human beta-2 microglobulin (beta2m) fused with HLA-A*2402-restricted human immunodeficiency virus type 1 (HIV-1) cytotoxic T-lymphocyte (CTL) epitopes (e-beta2m) in separate SeV vectors. When we coinfected nonhuman mammalian cells with the SeVs, naturally folded human MHC class I/peptide complexes were secreted in the culture supernatants. Biotin binding peptide sequences on the C terminus of the heavy chain were used to tetramerize the complexes. These tetramers made in the SeV system recognized specific CD8-positive T cells in peripheral blood mononuclear cells of HIV-1-positive patients with a specificity and sensitivity similar to those of MHC class I tetramers made in an Escherichia coli system. Solo infection of e-beta2m/SeV produced soluble e-beta2m in the culture supernatant, and cells pulsed with the soluble protein were recognized by specific CTLs. Furthermore, when cells were infected with e-beta2m/SeV, these cells were recognized by the specific CTLs more efficiently than the protein pulse per se. SeV is nonpathogenic for humans, can transduce foreign genes into nondividing cells, and may be useful for immunotherapy to enhance antigen-specific immune responses. Our system can be used not only to detect but also to stimulate antigen-specific cellular immune responses. 相似文献
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Very few types of normal cells fail entirely to express class I human leukocyte antigens (HLA), and many of those cells (sperm, fetal amnion epithelial cells, and fetal trophoblasts) are related to the process of reproduction. Susceptibility of sperm to modulation of class I antigens has not been examined, but it has recently been demonstrated that amnion cells respond to exposure to IFN-gamma with readily detectable levels of class I antigens. In addition, one of two trophoblast cell lines (BeWo) has been shown to exhibit enhanced expression of class I HLA in response to IFN-gamma. Expression by a second trophoblast cell line (Jar) was not inducible. Findings in the present study included demonstration of IFN-gamma-enhanced class I-specific mRNA synthesis in JEG-3 cells, which are derived from BeWo, and failure of synthesis by Jar cells. Those results eliminated trivial explanations for the preceding findings and confirmed the responsiveness of some but not all cells of trophoblast origin to IFN-gamma. When successful modulating conditions for amnion and malignant trophoblast cells were applied to normal tissues, third trimester term chorionic cytotrophoblasts and first trimester villous syncytial and cytotrophoblasts failed to exhibit class I HLA. Neither malignant nor normal trophoblasts expressed class II HLA under any condition of testing. Failure of induction of HLA expression by normal trophoblasts could not be attributed to either loss of viability by tissue explants or failure of modulating reagents to reach the trophoblasts. The results demonstrate that regulation of expression of histocompatibility antigens by major populations of normal trophoblasts and one of two choriocarcinoma cell lines differs markedly from that of other fetal and adult cells. Uncommon regulatory mechanisms may be essential to maintenance of the trophoblast as an immunologically inert barrier between the mother and her antigenically disparate fetus. 相似文献
16.
Lia M. E. Dobbe Nico J. Stam Jacques J. Neefjes Marius J. Giphart 《Immunogenetics》1988,27(3):203-210
Human serum was found to contain a variety of class I-like molecules by Western blotting with anti-class I heavy chain reagents: major bands usually are observed around M
r 44 000, 40 000, and 35 000–37 000. HLA-A24-positive individuals are distinguished by higher serum levels of M
r 44 000 and 40 000 class I-like molecules than those found in HLA-A24-negative individuals. The M
r 44 000 serum molecules are probably intact class I molecules that have been shed from the cell membrane, because they contain both a transmembrane segment (TM), as deduced from detergent-binding experiments, and a cytoplasmic tail (CT), as inferred from reactivity with an antipeptide serum specific for the cytoplasmic domain of class I antigens (RaCT). The M
r 35 000 and 37 000 molecules contain neither a TM nor a CT region and therefore are probably proteolytic breakdown products of cellular and/or serum M
r 44 000 molecules, although the existence of Q10-like molecules in man cannot be ruled out. The M
r 40 000 molecules do not contain a TM region. M
r 40 000 molecules reactive with the RaCT serum were found in the minority (2/13) of sera tested. We conclude that alternative splicing resulting in a precise excision of the TM exon plays a minor role in the generation of serum HLA class I antigens.Abbreviations used in this paper B2m
beta-2 microglobulin
- BSA
bovine serum albumin
- EBV-BLCL
Epstein-Barr virus-transformed B lymphoblastoid cell line
- mAb
monoclonal antibody
- SDS-PAGE
sodium dodecyl sulfate-polyacrylamide gel electrophoresis
- TCA
trichloroacetic acid 相似文献
17.
W C van Schooten T Maiore K R Jones L Paborsky 《Journal of immunology (Baltimore, Md. : 1950)》1992,148(4):1043-1048
An initial event in T cell activation is the specific adherence of T cells via their T cell receptor to the MHC peptide complex. We have studied this adherence by incubating T cells with preformed HLA DR4Dw4 peptide complexes attached to a solid support. Adherence of sodium 51Cr-labeled T cell clones specific for the influenza hemagglutinin peptide, HA 307-319, was maximal after 15 min and was specific for the HLA DR4Dw4-HA 307-319 complex. The binding was temperature dependent and could be blocked with azide or protein kinase C inhibitors, indicating that for adherence the T cells need to be metabolically active and have a functioning protein kinase C pathway. The adherence could be blocked with CD4- or CD3-reactive murine mAb, suggesting that the TCR and CD4 molecules work in concert to induce strong adherence to the HLA DR4Dw4-HA 307-319 complex. A subsequent event in T cell activation is proliferation, which is thought to need additional proteins such as IL-1 or other adhesion molecules. MHC peptide complexes coated on microtiter plates also induced proliferation in the human T cell clones. Removal of any monocytes by treatment of human T cell clones with anti-CD14 in conjunction with C, followed by purification over a nylon wool column, did not abrogate proliferation. After prolonged culture of the T cell clones in plates coated with peptide-pulsed HLA DR4Dw4 in the presence of IL-2, the T cell clones continued to proliferate in response to peptide. These results suggest that human T cell clones do not require a second signal from a monocyte or other APC to proliferate. 相似文献
18.
Filippo Vairo Pâmela Portela Patrícia H. Salim Mariana Jobim Cristina Netto Alicia Dorneles Suzana Mittlestadt Luiz Fernando Jobim Ida Vanessa D. Schwartz 《Gene》2013
Gaucher disease (GD) is caused by reduced activity of the lysosomal enzyme glucocerebrosidase, which leads to a buildup of glucocerebroside within the cells and chronic stimulation of the immune system. GD is associated with clinical variability even in the same family, which suggests the influence of modifier genes. Natural killer (NK) cells play an important role in the immune response, and their number is decreased in GD. Killer-cell immunoglobulin-like receptors (KIR) regulate the activity of NK cells through an interaction with specific human leukocyte antigen (HLA) class I molecules on target cells. 相似文献
19.
Khudiakova NE Novikov VV Kravchenko GA Ivanova NI Ptitsyna IuS Nosov NN 《Zhurnal mikrobiologii, epidemiologii, i immunobiologii》2004,(1):42-45
The levels of HLA, class I, antigen and HLA-DR antigen in the blood sera of HIV-infected persons were determined by the enzyme immunoassay. The levels of soluble antigens HLR-DR and of HLA, class I, in serum samples containing only antibodies to HIV were elevated, respectively, 1.8- and 1.3-fold in comparison with the norm. The level of soluble HLA-DR antigen in samples containing the markers of other infections (HBsAg, antibodies to hepatitis C virus, anti-IgM antibodies to cytomegalovirus) was significantly higher in comparison with samples containing only antibodies to HIV and serum samples from healthy donors (p < 0.05). The concentration of soluble HLA antigen, class I, in the samples containing antibodies to HIV and markers of other infections was also elevated, but the statistically authentic increase in comparison with the normal level was observed only in the presence of the markers of HIV infection, hepatitis C and cytomegalovirus infection. 相似文献