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1.
Summary The antigenic activity of the N-terminal region of coat protein of turnip mosaic virus (TuMV) aphid transmissible strain 1 and non-transmissible strain 31 was examined by using a panel of monoclonal antibodies (MAbs) raised against the two virus strains as well as antisera raised against several synthetic peptides from the N-terminal region of the protein. The reactivity of these antibodies was tested in ELISA and in a biosensor system (BIAcore Pharmacia) using virus particles, dissociated coat protein and synthetic peptides as antigens. Substitution of a single amino acid at position 8 in the coat protein of TuMV strain 1 abolished any cross-reactivity between MAbs to strain 1 and the substituted peptide (strain 31) in ELISA although some cross-reactivity was apparent in BIAcore inhibition experiments. In reciprocal tests with MAbs to strain 31 no cross-reactivity with the heterologous peptide was detected in either type of assay. The amino acid residue present at position 8 appears to play a critical role in the binding capacity of MAbs specific for the N-terminal region of TuMV. Antiserum to a synthetic peptide corresponding to residues 1–14 of the protein of TuMV strain 1 was found to react strongly with dissociated coat protein and intact virus particles and was able to inhibit the aphid transmission of the virus. Antiserum to the corresponding peptide of strain 31 did not have this capacity. 相似文献
2.
The feasibility of using antigen modifications and synthetic resin-bound peptides to distinguish closely related epitopes has been demonstrated in this report. Epitopes recognized by five monoclonal antibodies (MAbs) specific to Escherichia coli ribosomal protein S13 have been located near the C-terminus and N-terminus of the S13 molecule; these epitopes were characterized by modifications of antigens and by utilization of peptides of increasing length synthesized on aminomethyl crosslinked polystyrene resin. Three of these MAbs react with the C-terminal peptide S13(84-117) which has five Lys residues clustered within the last 16 amino acids. Phthalylation of Lys residues almost eliminated the binding of two MAbs and reduced binding of the third by 50%. Removal of the C-terminal Lys residue(s) at the S13 C-terminus with carboxypeptidase B has no effect on the binding of these three MAbs. A 23-residue peptide corresponding to S13(95-117) was synthesized by a modified Merrifield solid phase method. Samples of resin with peptides of increasing length were obtained after each cycle of amino acid coupling. The peptides were deprotected without hydrolysis of the peptide-resin linkage and used in an enzyme immunoassay to detect the extent of MAb interaction with the lengthening peptides. The epitopes recognized by the two MAbs more sensitive to Lys modification have been localized in S13(97-117). The third MAb binds to S13(98-117) but binds more strongly when the sequence is lengthened. Two MAbs directed toward the N-terminal 22 residues of S13 were similarly characterized. Binding of one MAb, little affected by phthalylation, required the N-terminal residue of S13 to be present in the synthetic peptide. The other MAb, whose binding was inhibited by phthalylation, bound to the synthetic S13(2-22) and bound more strongly to the synthetic S13(1-22). 相似文献
3.
Generation and characterization of monoclonal antibodies against dengue virus type 1 for epitope mapping and serological detection by epitope-based peptide antigens
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Chen YC Huang HN Lin CT Chen YF King CC Wu HC 《Clinical and Vaccine Immunology : CVI》2007,14(4):404-411
Dengue virus (DEN), the pathogen behind dengue hemorrhagic fever, remains a public health problem in Asia and South America. In this study, monoclonal antibodies (MAbs) against DEN serotype 1 (DEN-1) were generated by fusing NSI/1-Ag4-1 mouse myeloma cells with lymphocytes from BALB/c mice immunized with DEN-1. Twelve MAbs were found to react specifically to the DENs by enzyme-linked immunosorbent assay, immunofluorescence analysis, and immunoblotting analysis. Five MAbs, namely, DA4-7, DA6-7, DA9-5, DA10-2, and DA11-13, were found to react with envelope proteins of DEN-1. Two serotype-specific MAbs of DEN-1, DA6-7 and DA11-13, were further shown to neutralize DEN-1 infection by a plaque reduction neutralization test. The neutralizing epitopes of these MAbs were further identified from a random peptide library displayed on phage. Immunopositive phage clones reacted specifically with these MAbs and did not react with normal mouse serum. Epitope-based peptide antigens were proved able to detect antibodies in serum samples collected from DEN-1-infected patients but not in those taken from DEN-2-infected patients or healthy controls. We believe that these MAbs and neutralizing epitopes will provide information that will lead to the development of DEN-1 serotype-specific diagnostic reagents and vaccines. 相似文献
4.
A B Siddique N Ahlborg M Warsame P Perlmann K Berzins 《Clinical and experimental immunology》1999,116(3):493-499
Human antibodies to the repeat regions of the Plasmodium falciparum asexual blood stage antigen Pf155/RESA interfere with parasite growth in vitro, but the significance in this respect of antibodies to non-repetitive epitopes is less clear. In this study the levels of antibodies to a non-repetitive part of Pf155/RESA (residue 199-221) in malaria-exposed individuals were analysed, as was the parasite-inhibitory capacity of such antibodies. Residue 199-221 is of particular interest since it includes a sequence homologous to a cytoadherence-related motif from band 3. Sera from donors in Liberia and Tanzania were analysed for reactivity in ELISA with synthetic peptides together overlapping this part of Pf155/RESA. High antibody reactivity was observed in most of the sera with two peptides including residues 199-211 and 202-214, respectively. Specific antibodies were affinity-purified from selected sera using these peptide sequences and were shown to react with Pf155/RESA by immunofluorescence and Western blotting. The purified antibodies were furthermore shown to inhibit parasite growth in vitro. The results suggest that both repeat and non-repeat epitopes in Pf155/RESA elicit antibodies with potential to protect against malaria infection. 相似文献
5.
Immunochemical Characterization of the MPB70/80 and MPB83 Proteins of Mycobacterium bovis 总被引:13,自引:0,他引:13
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Harald G. Wiker Konstantin P. Lyashchenko A. Murat Aksoy Kenneth A. Lightbody John M. Pollock Sergiy V. Komissarenko Sergiy O. Bobrovnik Irina N. Kolesnikova Leonid O. Mykhalsky Maria L. Gennaro Morten Harboe 《Infection and immunity》1998,66(4):1445-1452
MPB70 and MPB80 (MPB70/80) and MPB83 are closely related antigens which are highly expressed in Mycobacterium bovis. MPB70/80 are soluble secreted antigens, while MPB83 is an exported lipoprotein associated with the bacterial surface. In the present study, these antigens had different mobilities in sodium dodecyl sulfate-polyacrylamide gel electrophoresis under reducing and nonreducing conditions. These differences may be explained by the fact that MPB70 and MPB83 both have two internal cysteine residues which would create ring structures by disulfide bonding. We analyzed the structures of MPB70/80 and MPB83 by using monoclonal antibodies (MAbs) raised against bovine purified protein derivative or whole M. bovis cells. MAb 1-5C reacted specifically with MPB70 and MPB80, and MAb MBS43 reacted specifically with MPB83, while the other antibodies, including several previously described MAbs, bound all three antigens. MAbs and polyclonal antibodies reacted strongly with reduced protein and less well with nonreduced protein, indicating involvement of linear epitopes. Epitopes of MAbs Bov-1, 2-6B, 1-5C, and 1-1D were mapped by using synthetic peptides of MPB70. Sequence comparison showed the peptide with the 1-5C-reactive epitope to have three residues different from those in the homologous region of MPB83. Exchanges of A for S in position 112 or Q for E in position 116 abolished the reactivity of MAb 1-5C. Polyclonal rabbit antibodies to native purified MPB70 reacted strongly with peptides 6, 7, and 8 of the N-terminal half of mature MPB70. Cattle sera of experimentally M. bovis-infected animals recognized a broader spectrum of peptides. These findings indicate that there is diagnostic potential for these proteins and that there is also a possible role for antibodies in elucidation of the host-mycobacterium relationship involving a surface-bound and exposed lipoprotein, MPB83, and its highly homologous soluble secreted MPB70/80 counterparts. 相似文献
6.
I. Dore D. Altschuh Z. Al Moudallal M. H. V. Van Regenmortel 《Molecular immunology》1987,24(12):1351-1358
The binding properties of 18 monoclonal antibodies (MAbs) directed against the tobacco mosaic virus (TMV) coat protein were studied with five related tobamoviruses and seven mutant viruses, as well as with the dissociated coat proteins of these variants. Ten of the antibodies bound to both TMV and TMV protein, but these were able to discriminate between different mutants only when whole virus particles were compared in the immunoassay. Three MAbs reacted with TMV but not with dissociated viral subunits and these recognized the same residue exchanges. Five MAbs recognized synthetic peptides of 13–28 residues corresponding to parts of the protein. By comparing the common accessible surface between TMV and antigenically related viruses, it was possible to narrow down the region recognized by some of these MAbs. The linear peptide sequence recognized by these antibodies did not represent the entire epitope and residue exchanges around this region were able to affect the binding of MAbs. 相似文献
7.
It has been inferred that residue changes that affect T cell recognition of synthetic peptides will have a similar effect in the intact protein. However, since small peptides do not require antigen processing it is possible that residue changes in synthetic peptides will not have an equivalent effect in the intact protein. Mutant proteins of staphylococcal nuclease (Nase) and 15mer synthetic peptides with corresponding substitutions were compared to determine if residue changes within an immunodominant epitope have an effect on the generation of naturally processed peptides. Five different substitutions in the synthetic peptide resulted in loss of reactivity of individual Nase-specific clones. When the same single amino acid changes were made in the intact protein, the naturally-processed peptides were also unable to stimulate the Nase-specific clones. However, two other substitutions in the synthetic peptide were stimulatory for a T cell clone even though the same changes in the intact protein were non-stimulatory. These results suggest that certain residue changes affect recognition of the naturally processed peptide but not the synthetic peptide with the same amino acid change. In addition, these results demonstrate that the effects of amino acid substitutions in synthetic peptides on T cell recognition may not always reflect the effects of these substitutions in the intact protein. Substitutions located outside Nase-specific T cell epitopes were also examined. Thirty different mutant proteins were all stimulatory. Moreover, a number of these mutants proteins were 50- to 100-fold more efficient in their stimulatory capacity than the native Nase protein.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
8.
The epitope structure of short ragweed allergen Amb a I (formerly antigen E or AgE) has been investigated by characterizing monoclonal antibodies (MAbs) from mice immunized with Amb a I. The MAbs to Amb a I that we previously produced and characterized (HaA1, HaB1 and HaC1) reacted with determinants which were conformationally dependent. Denaturation of Amb a I, which is a prerequisite for peptide isolation and hence epitope localization, destroyed these determinants. We report here the isolation of 15 MAbs produced against denatured Amb a I and present their reactivities with native Amb a I, denatured Amb a I, and peptide fragments of Amb a I. None of the 15 MAbs to denatured Amb a I bind to native Amb a I, as judged by their lack of binding to Amb a I in immune complex with HaA1 and HaC1. All 15 MAbs reacted with the extensively reduced and alkylated form of denatured Amb a I and 14 of the 15 were shown by Western blotting techniques and ELISA to have activity against the isolated alpha chain or beta chains of Amb a I, but not both. In addition, several MAbs react with tryptic fragments of Amb a I which allowed us to isolate and sequence two tryptic peptides of Amb a I. Antisera raised against KLH-coupled synthetic analogs of these peptides reacted well with intact, denatured Amb a I. Finally, during chromatographic purification of Amb a I from fresh pollen extracts, various MAbs began to react with Amb a I as a function of stage of isolation, suggesting that some proportion of Amb a I spontaneously denatures during purification, converting from the allergenic form possessing two major B cell epitopes to an allergenically inactive form. 相似文献
9.
Albert Bosch Juan F. Gonzlez-Dankaart Isabel Haro Rodrigo Gajardo Jos A. Prez Rosa M. Pint 《Journal of medical virology》1998,54(2):95-102
A new continuous epitope of hepatitis A virus (HAV) was defined in the VP3 protein. Convalescent sera recognised the synthetic peptide 3110–3121 (FWRGDLVFDFQV). The replacement of the arginine, glycine, or aspartic acid at positions 112, 113, or 114, respectively by other aminoacids induced the loss of synthetic peptide recognition by human convalescent sera, thereby confirming the presence of an epitope in the original VP3(110-121) sequence. Shorter VP3 peptides such as VP3(110-119), VP3(110-117), and VP3(110-116) and a tandem repeat of VP3(111-116) failed to react with convalescent sera, indicating the importance of the entire peptide in the epitope structure. The maximum inhibition of human convalescent binding to HAV by the VP3(110-121) peptide was around 60%, and 50% inhibition was achieved at a peptide concentration of 2.3–2.4 μg/ml. Antibodies generated by this peptide bound to intact HAV and neutralised its infectivity. Antipeptide antibodies inhibited convalescent serum binding to HAV. Monoclonal antibodies H7C27 and MAK-4E7 inhibited completely binding of the antipeptide antibodies to HAV. J. Med. Virol. 54:95–102, 1998. © 1998 Wiley-Liss,Inc. 相似文献
10.
Multiple reactivity of monoclonal antibodies 总被引:1,自引:0,他引:1
The reactivity of 31 purified monoclonal antibodies (MAbs) with 10 unrelated protein antigens was determined by an enzyme-linked immunosorbent assay. Twenty-two of the monoclonal antibodies (71%) reacted with at least one of these nonhomologous antigens. Overall, there was positive reactivity in 27% of the tests. A larger incidence of multiple reactivities was observed with increasing concentration of the MAbs. Certain of these antibodies (29%) did not react with any nonhomologous tested antigens, whereas others had reactivity with multiple antigens. Multiple reactivity was observed with 6 of 14 of the hybridomas in a test that measured binding to a cell line. Multiple reactivity was more frequently observed when the MAbs were tested with complex antigens, such as keyhole limpet hemocyanin or a cell surface. These experiments demonstrate that MAbs frequently react with multiple antigens. 相似文献
11.
Concentrated cell-free filtrates (nocardins) were prepared from Nocardia asteroides cultures grown on Sauton's synthetic broth. Nocardins from 10 strains of six N. asteroides serotypes were produced and the proteins separated by isoelectric focusing. N. asteroides antigens among these proteins were tested for specificity using rabbit antisera and monoclonal antibodies (MAbs) against N. asteroides and Mycobacterium tuberculosis by the enzyme-linked immunoelectrotransfer blot test. At least 15 protein antigens were identified from each of the 10 nocardins. The immunodominant antigens were one serotype-specific N. asteroides protein with an isoelectric point (pI) of 4.0 (factor 1) and two group antigens with pIs of 4.43 (factor 6) and 4.68 (factor 8). The nitrocellulose strips prepared with these antigens did not react with antibodies to M. tuberculosis, nor with normal sera from humans, rabbits, or mice, but reacted specifically with anti-N. asteroides MAbs and polyclonal antibodies. Four purified protein derivatives of tuberculin were tested and did not cross-react with the three anti-N. asteroides MAbs. These reactions suggest that the antigens identified as factors 1, 6 and 7 are specific to N. asteroides and that factor 1 is specific for serotype 2, while factors 6 and 8 are species-specific. 相似文献
12.
Four mouse monoclonal antibodies (MAbs) that react with filamentous M13KO7 and R408 phage were obtained. Three of these MAbs (two IgG2a and one IgG3) recognize linear sequences of the p8 main structural coat protein, and one (IgG2a) identifies a putatively conformational epitope, as suggested by Western blot. These MAbs also react with recombinant phage expressing peptide antigens fused to p8, and are though useful reagents for peptide/protein phage display screening based methods. The latter was shown in an enzyme-linked immunoadsorbent assay (ELISA) and a visual immunoassay where one of the anti-p8 MAbs was used to capture recombinant phages displaying a peptide characteristic of the Hepatitis B virus surface antigen or a Dengue virus-related peptide antigen. 相似文献
13.
Cells producing human antibodies to synthetic viral peptides MH-24 (corresponding to 302-325 residues of HIV-1 gp120) and p107 (main peptide of EBV antigen EBNA-1) were fused with human x mouse heteromyeloma B6B11. The efficacy of specific hybridization was 40%. Hybrid cells H1F2 (MN-specific) and HF4 (p107-specific) were cloned by the limiting dilutions method. Monoclonal antibodies (MAb) were tested in enzyme immunoassay on a panel of synthetic peptides. All resultant MAbs were polyspecific for tested synthetic peptides. The data permit a conclusion that previously detected polyspecificity of human cultural antibodies to virus peptides is due to the true polyspecificity of antigen-binding centers of MAb, but not to the presence of strange cells in the culture. 相似文献
14.
Anti-human milk fat globule membrane monoclonal antibodies HMFG-1 and HMFG-2 recognize epitopes within the protein core of human polymorphic epithelial mucin (PEM). These have been identified as PDTR and DTR, respectively. Using the solid phase synthesis of immobilized tetrameric peptides, we have systematically investigated the contribution of each amino acid in the immune recognition of the PDTR domain by the antibodies HMFG-1 and HMFG-2. The findings obtained have been interpreted with respect to the presence of, and requirements for elements of secondary structure, which have been identified in this region of the PEM protein core. 相似文献
15.
Two chicken monoclonal antibodies (MAbs), HU/Ch2-7 and HU/Ch6-1, against heterophil Hanganutziu-Deicher (HD) antigens with N-glycolylneuraminic acid (NeuGc) at a terminal carbohydrate were established by cell fusions using chicken B cell lines lacking thymidine kinase and spleen cells from chickens immunized with II3NeuGc alpha-LacCer (HD3). The reactivities of these MAbs against several gangliosides including NeuGc-containing glycosphingolipids were examined by a thin-layer chromatography/immunostaining method. MAb HU/Ch2-7 (IgG) reacted strongly with HD3 and IV3NeuGc alpha-nLc4Cer (HD5) and weakly with VI3NeuGc alpha-nLc6Cer (HD7) and 4-O-acetyl-HD3. HU/Ch6-1 (IgG) reacted with HD3 and HD5, but did not react with the other HD antigens. The reactivities of these MAbs against HD antigen were greatly reduced by pre-treatment of the antigen with neuraminidase. These MAbs did not react with N-acetylneuraminic acid-containing gangliosides (GM1 and GM3). These results indicate that these two chicken MAbs are directed toward the antigenic epitope containing the NeuGc. 相似文献
16.
Two monoclonal antibodies (MAbs) against apolipoprotein A-I (apo A-I), 6B9 and FF9B10, and one MAb against apolipoprotein A-II (apo A-II), 3F5, were characterized. To establish the epitope of apo A-I recognized by these antibodies, different experimental approaches were performed. First, competition between MAbs and the related epitopes on the same antigen was performed using double-determinant tests with previously characterized MAbs. Second, competition of different synthetic peptides of apo A-I in solution with apo A-I immobilized to solid phase was carried out. The MAbs against apo A-I (6B9 and FF9B10) appear to recognize discontinuous epitopes located in the amino-terminal region of the apo A-I. In competition experiments MAb 3F5 did not recognize central- or carboxy-terminal peptides of apo A-II. Furthermore, apo A-II was stronger recognized when it was included in HDL or LpA-I:A-II than in its purified form. So the epitope for 3F5 is better expressed in the lipoprotein structure. Finally, to establish the epitopes expression in different antigens in solution, competition of purified apo A-I, apo A-II, LpA-I, and LpA-I:A-II particles or HDL3, with apo A-I or HDL immobilized to solid phase, was carried out. The results showed that both MAbs against apo A-I reacted with poor affinity against free apo A-I, with high and similar affinities against Lp A-I and Lp A-I:A-II lipoparticles and with the highest affinity against HDL3. The MAb 3F5 against apo A-II recognized only LpA-I:A-II and not LpA-I lipoparticles. 相似文献
17.
Interferon tau (IFNtau) produces an array of biological effects, including antiluteolytic, antiviral, antiproliferative and immunomodulatory activities, without the consequent cytotoxicity associated with other type I IFNs. Four anti-IFNtau monoclonal antibodies (MAbs) have been characterized by determining regional epitopes and observation of their effects on IFNtau binding, antiviral and antiproliferative activity. Using an enzyme-linked immunoadsorbent assay (ELISA) developed against six overlapping synthetic peptides representing the entire linear sequence of IFNtau, three antibodies, HL-98, HL-100 and HL-127, were found to react with the carboxy terminal peptide, while HL-129 bound the penultimate amino terminal peptide. Binding studies indicated that MAbs directed against either region could effectively inhibit the binding of alkaline phosphatase labeled IFNtau to cells expressing type I IFN receptors. While only two of the MAbs significantly reversed IFNtau-induced growth inhibition, the antiviral activity of IFNtau was significantly inhibited by MAbs that bound the amino and carboxy termini, confirming the functional importance of these domains in the binding and subsequent activity of IFNtau. 相似文献
18.
Rahbarizadeh F Rasaee MJ Forouzandeh M Allameh A Sarrami R Nasiry H Sadeghizadeh M 《Immunological investigations》2005,34(4):431-452
Camelidae are known to produce immunoglobulins (Igs) devoid of light chains and constant heavy-chain domains (CH1). Antigen-specific fragments of these heavy-chain IgGs (VHH) are of great interest in biotechnology applications. This paper describes the first example of successfully raised heavy-chain antibodies in Camelus dromedarius (single-humped camel) and Camelus bactrianus (two-humped camel) against a MUC1 related peptide that is found to be an important epitope expressed in cancerous tissue. Camels were immunized against a synthetic peptide corresponding to the tandem repeat region of MUC1 mucin and cancerous tissue preparation obtained from patients suffering from breast carcinoma. Three IgG subclasses with different binding properties to protein A and G were purified by affinity chromatography. Both conventional and heavy-chain IgG antibodies were produced in response to MUC1-related peptide. The elicited antibodies could react specifically with the tandem repeat region of MUC1 mucin in an enzyme linked immunosorbant assay (ELISA). Anti-peptide antibodies were purified after passing antiserum over two affinity chromatography columns. Using ELISA, immunocytochemistry and Western blotting, the interaction of purified antibodies with different antigens was evaluated. The antibodies were observed to be selectively bound to antigens namely: MUC1 peptide (tandem repeat region), human milk fat globule membrane (HMFG), deglycosylated human milk fat globule membrane (D-HMFG), homogenized cancerous breast tissue and a native MUC1 purified from ascitic fluid. Ka values of specific polyclonal antipeptide antibodies were estimated in C. dromedarius and C. bactrianus, as 7 x 10(10) M(-1) and 1.4 x 10(10) M(-1) respectively. 相似文献
19.
Ponce-Bravo S Ledesma-Montes C Morales-Sánchez I 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2008,116(2):93-98
The aim of this study was to determine the immunoexpression of normal salivary gland cells using two human milk fat globule membrane protein antibodies (HMFG-1 and HMFG-2). Paraffin-embedded, 5 microm-thick slides from parotid and submandibular gland tissues were cut and immunostained with monoclonal antibodies HMFG-1 and HMFG-2 against MUC1 protein. HMFG antigens were found in secretory epithelial cells and ductal cells lining the striated and intercalated ducts in the intraductal secretion material, and sometimes in the myoepithelial cells. Our results suggest that HMFG-1 and HMFG-2 proteins may play a role in normal salivary gland function, mainly in the manufacturing and secretion of saliva. 相似文献
20.
Immunohistochemical characterization of fibrin(ogen)-related antigens in human tissues using monoclonal antibodies 总被引:4,自引:0,他引:4
A Bini R Mesa-Tejada J J Fenoglio B Kudryk K L Kaplan 《Laboratory investigation; a journal of technical methods and pathology》1989,60(6):814-821
A new approach to study the distribution of fibrin(ogen)-related antigens was investigated using three different monoclonal antibodies (MAbs) and the avidin-biotin complex immunoperoxidase technique. MAb I8C6 recognizes B beta 1-42 peptide and can react with either fibrinogen or fibrin I; MAb T2G1 recognizes B beta 15-42 peptide and detects fibrin II but does not cross-react with fibrinogen; MAb GC4 reacts with Fragments D/DD derived from plasmin degradation of fibrinogen or fibrin but not with intact fibrinogen. The method can be applied to frozen or Bouin's fixed paraffin-embedded tissues obtained at biopsy, surgery, and autopsy. The distribution of the three antigens observed with the three MAbs was compared with that obtained with a polyclonal antiserum to fibrinogen and with the more conventional histochemical stains used in pathology to demonstrate fibrin deposits in tissues (Lendrum and PTAH). The staining observed with the three monoclonals clearly detected three different populations of fibrin(ogen)-related antigen in the tissues examined. The staining with MAb T2G1 specifically detected fibrin II with greater sensitivity than did conventional stains. The results of this study suggest that this method allows the molecular form of fibrin(ogen)-related deposits in tissues to be determined and this information may help to elucidate the role of fibrin in various disease states, such as atherosclerosis and renal disease, and in tumor growth and metastasis. 相似文献