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991.
Model systems to study the parameters determining the success of phage antibody selections on complex antigens 总被引:4,自引:0,他引:4
Mutuberria R Hoogenboom HR van der Linden E de Bruïne AP Roovers RC 《Journal of immunological methods》1999,231(1-2):65-81
Phage antibody display technology offers a powerful tool for the isolation of specific antibodies to defined target antigens. Most selection strategies described to date have relied on the availability of purified and often recombinant antigen, providing the possibility to perform selections on a well-defined antigen source. However, when the target antigen cannot be purified (e.g., an integral membrane protein), or if the antigen is unknown (e.g., when searching for novel markers on cells or tissues), panning of phage antibody libraries has to be performed on complex antigen sources such as cell surfaces or tissue sections, or even by in vivo selection methods. This provides a series of technical and experimental challenges. One focus of our research is to select antibodies directed to novel cancer-induced antigens expressed by tumours and by the tumour vasculature. To understand the parameters governing selection on complex antigen sources and to assess the efficiency of these phage library selections, we have set up two model selection systems in which both tumour cells and vascular endothelial cells serve as target "antigen". We describe a model based on phage antibodies directed to the tumour antigen epithelial glycoprotein-2, to compare phage antibody selections on a range of different antigen sources including purified and recombinant antigen, whole live cells, tissue cryosections and in vivo grown solid tumours. Secondly, we describe a model based on a phage antibody directed against the endothelial cell inducible adhesion molecule E-selectin. We compare selections on cultured cell monolayers with selections on cell suspensions immobilised on columns, to determine which selection approach is most suitable for the identification of novel tumour endothelial cell markers. Our data provide insight into the efficiency and thus potency of different selection strategies and show that there are very large differences in the recovery and enrichment of binding phage between the different methods tested. Our results further demonstrate the feasibility of phage antibody selections on whole, intact cells and show that these may sometimes compare favourably to selections on purified antigen. Selections on endothelial cells immobilised on columns compare favourably with selections on cell-monolayers; the most favourable conditions for both selection procedures are described. The implications of our data for phage antibody selections on these different complex antigen sources using either non-immune or immune phage antibody repertoires are discussed. The use of model systems such as the ones described here will help to determine optimal experimental conditions for phage library selections on complex antigens and aid in developing more powerful selection procedures for target discovery. 相似文献
992.
Louis Journeau Marc-Antoine Pistorius Ulrique Michon-Pasturel Marc Lambert Francois-Xavier Lapébie Alessandra Bura-Riviere Philippe de Faucal Patrick Jego Quentin Didier Cécile Durant Geoffrey Urbanski Baptiste Hervier Claire Toquet Christian Agard Olivier Espitia 《Autoimmunity reviews》2019,18(5):476-483
993.
Schwienbacher I Fendt M Schnitzler HU 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》2005,160(4):538-544
The acoustic startle response is enhanced during states of fear and attenuated during pleasant ones. Our question was whether pharmacological stimulation of the reward system disrupts the learning and retrieval of conditioned fear as measured by fear-potentiated startle. We therefore injected the dopamine agonist amphetamine into the nucleus accumbens (NAC) immediately before either acquisition or expression of conditioned fear and measured the effect of these injections on fear-potentiated startle and baseline startle response. This study clearly showed that amphetamine injections into the NAC had no effect on baseline startle amplitude and acquisition/expression of conditioned fear. In contrast, amphetamine injections into the nucleus accumbens clearly enhanced spontaneous motor activity. These results suggest that dopamine within the NAC is not involved in modulation of fear-potentiated startle and baseline startle. 相似文献
994.
Eimeria tenella microneme protein EtMIC3: identification, localisation and role in host cell infection 总被引:1,自引:0,他引:1
Labbé M de Venevelles P Girard-Misguich F Bourdieu C Guillaume A Péry P 《Molecular and biochemical parasitology》2005,140(1):43-53
The gene coding for Eimeria tenella protein EtMIC3 was cloned by screening a sporozoite cDNA library with two independent monoclonal antibodies raised against the oocyst stage. The deduced sequence of EtMIC3 is 988 amino acids long. The protein presents seven repeats in tandem, with four highly conserved internal repeats and three more divergent external repeats. Each repeat is characterised by a tyrosine kinase phosphorylation site, WRCY, and a reminiscent motif of the thrombospondin1 (TSP1)-type I domain, CXXXCG. The protein EtMIC3 is localised at the apex of free parasite stages. It is not detected in the early intracellular parasite stage but is synthesised in mature schizonts. Secretion of the protein is induced when sporozoites are incubated in complete medium at 41 degrees C. Strangely enough, the two independent mAb that allow cloning of EtMIC3 interfere with parasitic growth in different ways. One is able to inhibit parasite invasion whereas the other inhibits development. Expression and localisation of the protein EtMIC3 are consistent with a protein involved in the invasion process as is expected for a microneme protein. 相似文献
995.
Small volume hypertonic resuscitation is a relatively new conceptual approach to shock therapy. It was originally based on the idea that a relatively large blood volume expansion could be obtained by administering a relatively small volume of fluid, taking advantage of osmosis. It was soon realized that the physiological vasodilator property of hypertonicity was a useful byproduct of small volume resuscitation in that it induced reperfusion of previously ischemic territories, even though such an effect encroached upon the malefic effects of the ischemia-reperfusion process. Subsequent research disclosed a number of previously unsuspected properties of hypertonic resuscitation, amongst them the correction of endothelial and red cell edema with significant consequences in terms of capillary blood flow. A whole set of actions of hypertonicity upon the immune system are being gradually uncovered, but the full implication of these observations with regard to the clinical scenario are still under study. Small volume resuscitation for shock is in current clinical use in some parts of the world, in spite of objections raised concerning its safety under conditions of uncontrolled bleeding. These objections stem mainly from experimental studies, but there are few signs that they may be of real clinical significance. This review attempts to cover the earlier and the more recent developments in this field. 相似文献
996.
We have identified, in a patient with atopic dermatitis, a consistent population of peripheral blood lymphocytes expressing a CD3+ gamma/delta TCR complex, while being unreactive with CD2. Further immunofluorescence studies showed that these cells almost completely co-express CD29 and CD45RA and have high membrane levels of CD11a compared to the alpha/beta TCR T cells. Neither a genetic influence nor an acute or reactivated herpesvirus infection were found to be related to the expanded gamma/delta T-cell subpopulation. Our data confirm the previous observations regarding the presence in the peripheral blood of an expanded gamma/delta TCR, CD2- subset and show that these cells have a peculiar phenotypic profile. The reasons for this expansion are, however, still unknown. 相似文献
997.
Sister chromatid exchange (SCE) frequency and cell proliferation were examined in lymphocyte cultures from a group of newborns, a group of elderly subjects and from patients with syndromes who exhibit progeriform characteristics (progeria, Cockayne syndrome, Rothmund-Thomson syndrome and Christ-Siemens-Touraine syndrome) by using the bromodeoxyuridine incorporation differential staining technique. We observed a significantly increase in basal SCE frequency and a less intensive cell proliferation in cultures from elderly subjects than from newborns, as shown by the significant increase in percentage of cells in first generation simultaneous with a reduction of cells in more advanced generations. Lymphocyte cultures from each one of the patients studied also showed a decreased cell proliferation in relation to their respective control and to newborn cultures. Each of these syndromes showed higher baseline SCE levels than the control and than the newborn and elderly groups. Only the patient with progeria showed values similar to those for the elderly group. Thus, in addition to showing clinical characteristics similar to those observed during the normal aging process, these progeriform syndromes also show cytogenetic characteristics similar to those of older individuals. 相似文献
998.
Lymphoid and non-lymphoid cells in the adenoid of children with otitis media with effusion: a comparative study 总被引:1,自引:0,他引:1 下载免费PDF全文
E B van Nieuwkerk C J de Wolf E W Kamperdijk S van der Baan 《Clinical and experimental immunology》1990,79(2):233-239
We characterized on immuno- and enzymecytochemical level the lymphoid and non-lymphoid cells in the adenoid of children with upper respiratory tract infections (URI) and otitis media with effusion (OME) and compared these with the adenoid of children with URI without OME and with the adenoid of 'healthy' children and adults. Besides macrophages and dendritic cells we also showed the presence of MHC class II positive, ciliated, epithelial cells. These non-lymphoid cells were present in all adenoids. However, their number was less than 1% of all cells. We found no difference in lymphocyte subsets from children with URI + OME compared with those from children with URI alone. These two groups showed a significant decrease of CD8-positive (suppressor/cytotoxic) cells and a slight increase in CD22-positive B cells in comparison to 'healthy' children. No difference was found in percentages of CD4-positive (helper/inducer) cells. The localization of the lymphoid subsets in adenoids of children with URI and/or OME did not differ from those of 'healthy' children and adults. 相似文献
999.
Insulin-specific T cell hybridomas derived from (H-2b x H-2k)F1 mice preferably employ F1-unique restriction elements for antigen recognition 总被引:11,自引:0,他引:11
T cell hybridomas of (B10 X B10.BR)F1 genotype with reactivity to bovine insulin (BI) were established to analyze the restriction and antigen fine specificity of (H-2b X H-2k)F1 T cells towards BI. Our data indicate a focusing of the response on two epitopes on the insulin molecule, the A chain loop determinant comprising amino acids A8 and A10, as well as the glutamic acid residue in position 4 of the A chain. Both were recognized either separately or in conjunction. Unexpectedly, the T cell hybridomas exhibited a marked preference for recognizing insulin in the context of F1-unique restriction elements of Ab alpha Ak beta type rather than parental high-responder I-Ab molecules. Analysis of the response of primed lymph node T cells of (B10 X B10.BR)F1 mice towards BI corroborated the finding of a preponderant corecognition of F1-unique I-A molecules. 相似文献
1000.
Production of fimbrial adhesins K99 and F41 by enterotoxigenic Escherichia coli as a function of growth-rate domain. 总被引:5,自引:5,他引:5 下载免费PDF全文
H W van Verseveld P Bakker T van der Woude C Terleth F K de Graaf 《Infection and immunity》1985,49(1):159-163
The production of fimbrial adhesins K99 and F41 by enterotoxigenic Escherichia coli has been measured in steady-state chemostat experiments at various specific growth rates (microseconds) and in a recycling fermentor across a range of mu values falling to less than 0.004 h-1. It has been demonstrated that the production of K99 and F41 fimbriae is correlated with mu both in aerobic and anaerobic chemostat experiments. A significant production of fimbriae was only detected at mu values higher than 0.2 h-1. This behavior was further examined by culturing the bacteria in a recycling fermentor with complete biomass retention. It could be shown that the production of K99 and F41 fimbriae only occurred during balanced growth, with a high biomass yield at mu values higher than 0.04 h-1 corresponding to mass doubling times (td) of less than 17 h. The production of both fimbriae halted during balanced growth with a lower biomass yield (at mu values between 0.012 and 0.04 h-1 corresponding to td values between 17 and 58 h) and unbalanced stringent growth (at mu values lower than 0.012 h-1 or td values higher than 58 h). The external pH of the medium greatly influenced the production of both K99 and F41 fimbriae. At pH values lower than 7, the production of fimbriae was strongly inhibited. Also, at pH values higher than 7, a decrease in production was observed. The consequences of the observed phenomena for the pathogenic behavior of this E. coli strain are discussed. 相似文献