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Showing papers on "Antigen published in 1980"


Patent
04 Aug 1980
TL;DR: In this article, two-site or "sandwich" immunometric assay techniques for determination of the presence and/or concentration of antigenic substances in fluids using monoclonal antibodies are described and compared to conventional assays using polyclonal antibodies.
Abstract: "Two-site" or "sandwich" immunometric assay techniques for determination of the presence and/or concentration of antigenic substances in fluids using monoclonal antibodies are described and compared to conventional assays using polyclonal antibodies. Also described are inhibition assays using complexes of antigens with a monoclonal antibody.

1,540 citations


Journal ArticleDOI
01 Apr 1980-Cell
TL;DR: The precise dissection of cellular mechanisms and interactions involved in the generation of human T cell responses has been facilitated in recent years by advances in four areas: first, the development of in this paper.

1,435 citations


Journal Article
TL;DR: Removal of the B1 positive population in peripheral blood eliminated all B cells capable or responding to pokeweed mitogen by maturation to Ig-producing cells.
Abstract: A human B lymphocyte-specific antigen (B1) was identified and characterized by the use of a monoclonal antibody. By indirect immunofluorescence, cytotoxicity, and quantitative absorption, B1 was present on approximately 9% of the peripheral blood mononuclear cell fraction and >95% of B cells from blood and lymphoid organs in all individuals tested. Monocytes, resting and activated T cells, null cells, and tumors of T cell and myeloid origin were B1 negative. B1 was distinct from standard B cell phenotypic markers, including Ig and Ia antigen. Removal of the B1 positive population in peripheral blood eliminated all B cells capable or responding to pokeweed mitogen by maturation to Ig-producing cells.

1,051 citations


Journal Article
TL;DR: Evidence is presented for two populations of Ia-like molecules on the human B cell line Raji, and monoclonal antibodies, L203 and L227, are described, which recognize nonpolymorphic determinants on B cell antigens.
Abstract: Evidence is presented for two populations of Ia-like molecules on the human B cell line Raji. Two monoclonal antibodies, L203 and L227, are described. Both recognize nonpolymorphic determinants on B cell antigens. Both immunoprecipitate 34,000- and 28,000-dalton material from 125I-labeled extracts of Raji, but L227 precipitates 25,000-dalton material as well. Immunodepletion experiments confirm that the antibodies react with two different populations of molecules.

1,040 citations


Journal ArticleDOI
01 Aug 1980-Blood
TL;DR: Analysis of CFU-F proliferative status by the thymidine suicide technique indicated that this cell was noncycling in individuals with undisturbed bone marrow function and data support the conclusion that the colonies described in this study are of fibroblastic nature.

882 citations


Journal Article
TL;DR: Five rat monoclonal antibodies have been derived that express specificities for determinants present on the molecular complex bearing the Lyt 2 antigen, which can block the cy tolytic activities of 5-day MLC cells or of cloned cytolytic T cells in the absence of C.
Abstract: Five rat monoclonal antibodies have been derived that express specificities for determinants present on the molecular complex bearing the Lyt 2 antigen. SDS-polyacrylamide gel electrophoresis of 125I-labeled polypeptides precipitated by each of these antibodies reveal 3 components (150,000, 75,000, and 33,000 daltons), and 2 components (44,000 and 33,000 daltons) when analyzed under nonreducing and reducing conditions, respectively. Two of these antibodies are IgG and are specific for the Lyt 2.2 determinant; the other 3 are IgM and react with determinants other than Lyt 2.2, which are nonpolymorphic. Each of the 5 antibodies can block the cytolytic activities of 5-day MLC cells or of cloned cytolytic T cells in the absence of C. Treatment of responding spleen cells with any of these antibodies and C inhibits the generation of cytolytic activity in MLC.

802 citations


Journal Article
TL;DR: Findings provided additional support for the notion that OKM1 was reactive with monocytes, and appeared to define two distinct populations of monocytes; an adherent population of large cells bearing surface Ia determinants and a nonadherent population of small, Ia-negative cells.
Abstract: A monoclonal antibody directed at a determinant on human peripheral blood monocytes was produced and characterized. This hybridoma antibody, termed OKM1, was reactive by indirect immunofluorescence and complement- (C) mediated lysis with adherent mononuclear cells. OKM1 was unreactive with lymphocytes, thymocytes, lymphoblastoid cell lines, and tumor cells of the T or B cell lineage. In contrast, acute myelomonocytic leukemia cells and granulocytes were reactive with the antibody. Pretreatment of peripheral blood mononuclear cells with OKM1 and C before culture with soluble antigens totally abolished their antigen-induced proliferative response. This function was restored by addition of 1% adherent cells. These findings provided additional support for the notion that OKM1 was reactive with monocytes. In addition, OKM1 appeared to define two distinct populations of monocytes; an adherent population of large cells bearing surface Ia determinants and a nonadherent population of small, Ia-negative cells. These OKM1+ Ia- cells were found to be a contaminant of most fractionated mononuclear cell subsets including the E-SIg-Null cell population.

795 citations


Journal Article
TL;DR: Strain distribution analyses so far indicate that the public specificities detected by these monoclonal antibodies are considerably different from those that had been established by traditional serology, which may have important implications relating to the structure and evolution of MHC gene products.
Abstract: Hybridoma cell lines secreting antibodies to mouse H-2 or Ia antigens have been generated by fusing mouse immune lymphocytes with appropriate myeloma lines. Among the 11 established clones reported here, nine produce anti-H-2 antibodies and two produce anti-Ia antibodies. The specificities and cross-reactions of these monoclonal antibodies have been studied in detail. One hybridoma antibody reacted only to Kk antigens without any detectable cross-reactions, thus suggesting reaction to a private specificity of the Kk molecule. All other anti-H-2 hybridoma antibodies appeared to detect public specificities as defined either by reactions with products of more than one H-2 locus or with different alleles at one or more loci. The two anti-Ia antibodies both reacted with I-E/C products, but exhibited different cross-reactivity patterns. Strain distribution analyses so far indicate that the public specificities detected by these monoclonal antibodies are considerably different from those that had been established by traditional serology. Since public specificities defined by the hybridoma antibodies must by definition represent cross-reactions, these findings may have important implications relating to the structure and evolution of MHC gene products.

791 citations


Journal ArticleDOI
07 Feb 1980-Nature
TL;DR: The present report describes the generation and characterisation of a monoclonal antibody specific for a common ALL antigen (CALLA) previously identified by conventional heteroantisera.
Abstract: Previous studies by Greaves1 and others2–6 have demonstrated the existence of an antigen associated with cells from many patients with acute lymphoblastic leukaemia (ALL) and some patients with chronic myelocytic leukaemia (CML) in blast crisis. Antisera to this common ALL antigen (CALLA) have been produced in rabbits and require extensive absorption which limits both the titre and quantity of antisera that can be generated and may result in variable specificity in different laboratories. The method for generation of specific antibody by somatic cell hybridisation introduced by Kohler and Milstein7 has been successfully used to produce monoclonal antibodies against various normal human cell-surface proteins, including β2 microglobulin8, histocompatibility antigens9, thymocyte and peripheral T-cell antigens10–12 and Ia-like antigens13. The present report describes the generation and characterisation of a monoclonal antibody specific for a common ALL antigen (CALLA) previously identified by conventional heteroantisera.

729 citations


Journal ArticleDOI
TL;DR: This work has shown that T lymphocytes with the capacity to recognize specific antigens, execute effector functions, and regulate the type and intensity of virtually all cellular and humoral immune respon...
Abstract: HUMAN T lymphocytes are endowed with the capacity to recognize specific antigens, execute effector functions, and regulate the type and intensity of virtually all cellular and humoral immune responses.1 Two major functionally distinct subsets of T cells have been defined with heteroantiserums, autoantibodies, and monoclonal antibodies directed at stable cell-surface antigens.2 3 4 5 6 7 8 Both have been independently programmed for their respective inducer (helper) and cytotoxic/suppressor functions during intrathymic differentiation. This review focuses on the biology of human regulatory T-cell subpopulations in health and disease. Development of T Lymphocytes A thymic microenvironment is necessary for the differentiation of T cells in all species. . . .

682 citations


Journal ArticleDOI
TL;DR: Antigenic materials were extracted from Campylobacter fetus subsp.
Abstract: Antigenic materials were extracted from Campylobacter fetus subsp. jejuni strains by heating bacterial suspensions in saline at 100 degrees C and by exposure to ethylenediaminetetraacetic acid. The antigens were heat stable at 100 degrees C, capable of sensitizing sheep erythrocytes for agglutination in antisera, and able to elicit production of specific antibody in rabbits; they occurred with different immunological specificities in 23 strains. Antisera against the 23 strains could be used for discriminating among isolates of the species when the passive hemagglutination technique was used for serotyping. Three serotypes were more common than others among a collection of human isolates.

Journal ArticleDOI
TL;DR: Enzyme-linked immunoadsorbant assays have been developed for types I, II, III, and IV collagen and for laminin and fibronectin and offer a specific, sensitive, and convenient method for the measurement of various connective tissue components either separately or simultaneously.

Journal ArticleDOI
TL;DR: Six distinct antigenic systems were defined by direct serological assays and absorption tests with a panel of 41 cell lines derived from normal and malignant human tissues, finding each has a distinctive pattern of distribution on various cell types, varying from a broad representation to a more restricted occurrence.
Abstract: Eighteen mouse monoclonal antibodies were selected for reactivity with cell surface antigens of the immunizing human melanoma cell line SK-MEL-28. Six distinct antigenic systems were defined by direct serological assays and absorption tests with a panel of 41 cell lines derived from normal and malignant human tissues. Biochemical analysis indicated that two of the antigens are glycoproteins with molecular sizes of 95,000 and 150,000 daltons (gp95 and gp150). Two other antigenic systems (O5 and the R24 group) are associated with heat-stable molecules having the characteristics of glycolipids. The remaining two antigens (M19 and R8) are heat labile, but molecular characterization has not been possible. Each of the antigenic systems has a distinctive pattern of distribution on various cell types, varying from a broad representation to a more restricted occurrence. O5 appears to be a species antigen, being present on virtually every human cell type tested. gp95, gp150, M19, and R8 are found on a characteristic proportion of melanomas, astrocytomas, and epithelial cancers and on normal kidney cells. The antigen defined by the R24 antibody has the most restricted distribution of all. Reactivity is found with melanomas and astrocytomas, whereas epithelial cell types, fibroblasts, and cells of hematopoietic origin lack R24. Although occurrence of gp95, gp150, M19, and R8 distinguishes a small subset of melanomas not expressing these antigens, R24 is found on all melanoma cells.

Journal ArticleDOI
TL;DR: The overall conclusion from the study is that for an understanding of the binding of antibody to cell-surface antigens the kinetics of the interaction are of major importance and theories based on equilibrium binding are inappropriate.
Abstract: The reaction kinetics of 125I-labelled mouse monoclonal antibodies binding to three cell-surface antigens of rat thymocytes (Thy-1.1, W3/25) were studied. The differences between bivalent and univalent interactions were determined by using antibody in the F(ab')2 or Fab' form and by using antigen in polymeric or monomeric forms. Association rate constants (k+1), dissociation rate constants (k-1) and equilibrium constants were determined. Also, the dissociation kinetics of rabbit antibodies against rat Thy-1 antigen were studied. The major findings were as follows. (i) With F(ab')2 antibody there was no simple relationship between antigen density at the cell surface and extent of bivalent binding. Extensive univalent binding was observed unless the antibody had a high k-1 for the univalent interaction, in which case all binding was bivalent. (ii) k+1 values were similar for F(ab')2 or Fab' antibody, and for the different antibodies were in the range 0.8 x 10(5)--1.1 x 10(6) M-1.s-1. These differences were sufficient to affect the interpretation of serological assays with the different antibodies. (iii) Antibody bound bivalently dissociated much more slowly than that bound univalently. However, the k-1 values for the univalently bound antibody were sufficiently low in most cases that the lifetime of the univalent complex was similar to or greater than the time needed for the assay. Thus the results could be interpreted on the basis of irreversible reactions. The overall conclusion from the study is that for an understanding of the binding of antibody to cell-surface antigens the kinetics of the interaction are of major importance and theories based on equilibrium binding are inappropriate.

Journal ArticleDOI
TL;DR: It is found that even among splenic and lymph node T cells subpopulations exist that tend to be either high Thy-1 and low Lyt-1 or vice versa; however, in agreement with previous studies, it is also found that LyT-2+3+ cells are more difficult to depelete with anti-Lyt-1 than Lyt+2-3- cells.
Abstract: Using monoclonal antibodies and multiparameter fluorescence analyses, we show that the expression of Lyt-1, Lyt-2, and Lyt-3 on T cell subpopulations is more complex than was originally recognized by the cytotoxic depletion studies with conventional reagents that defined the Lyt-1+2+3+, Lyt-1+2-3-, and Lyt-1-2+3+ populations. We detect at least some Lyt-1 on all T (Thy-1-bearing) lymphocytes; however, in agreement with previous studies, we find that Lyt-2+3+ cells are more difficult to depelete with anti-Lyt-1 than Lyt-1+2-3- cells. Surprisingly, we found a small subpopulation of cells carrying relatively large amounts of Lyt-1 and no Thy-1 detectable by fluorescence-activated cell sorter analysis. We also detect cells with this phenotype histologically in B cell zones (primary follicles) and germinal centers in spleen and lymph nodes. In general, the Lyt-1 only population represents approximately 2% of spleen cells. The relative quantitative expression of Thy-1, Lyt-1, Lyt-2, and Lyt-3 changes systematically during T cell maturation. Among Lyt-1+2+3+ cells in the thymus, Thy-1 and Lyt-2 are high, whereas Lyt-1 is low. Among splenic T cells, in contrast, Thy-1 is low, Lyt-1 is high, and Lyt-2 and Lyt-3 are a little higher than in thymus. In general, Thy-1 expression is negatively correlated with Lyt-1. Thus, even among splenic and lymph node T cells subpopulations exist that tend to be either high Thy-1 and low Lyt-1 or vice versa. Lyt-2+3+ cells represent approximately 85% of thymocytes but only approximately 35% of splenic or lymph node T cells. The Lyt-2+3+ cells are found predominantly in the low Lyt-1, high Thy-1 subpopulation.

Journal ArticleDOI
TL;DR: Three types of antibodies appeared to be highly specific for scleroderma: antibody to Scl-70 antigen, antibody to centromere, and antinucleolar antibody, and the anti-centromere antibody appeared to been highly selective for the CREST variant of progressive systemic sclerosis.
Abstract: Antinuclear antibodies wer demonstrated in the sera of 43 of 45 (96%) patients with progressive systemic sclerosis (22 of 24 with diffuse scleroderma and 21 of 21 with the CREST syndrome variant). This high percentage of positive reactions resulted from the use of a tissue culture substrate (Hep-2) to detect antinuclear antibodies by the indirect immunofluorescent method. Patterns of nuclear staining included diffuse fine speckles, large coarse speckles, nucleolar and centromere staining. When organ sections such as mouse kidney were used as substrate for the detection of antinuclear antibodies, nucleolar staining and centromere staining were the two patterns most frequently overlooked. Three types of antibodies appeared to be highly specific for scleroderma: antibody to Sc1-70 antigen, antibody to centromere, and antinucleolar antibody. The anti-centromere antibody appeared to be highly selective for the CREST variant of progressive systemic sclerosis.

Journal Article
TL;DR: The occurrence of a population of cells with several functional and structural features of macrophages among the lipid-laden cells of experimental diet-induced arterial lesions suggests that some foam cells may be derived from monocytes.
Abstract: A variable population of fat-filled "foam" cells in diet-induced experimental arterial intimal plaques of rabbits and monkeys were analyzed for several features characteristic of macrophages. These included: 1) surface binding and phagocytosis of antibody-coated or complement-coated erythrocytes to detect specific surface receptors; 2) cytochemical tests and ultrastructural features to evaluate cell function and structure; and 3) rapid adherence to glass, a feature of macrophage activity, to isolate and identify a homogeneous population of fat-filled foam cells from excised and disrupted arterial lesions. Mixed populations of cells grown in culture from explants of lesions were also analyzed and lipid-filled cells were studied in histologic sections of adjacent lesions. Eighty to ninety percent of the easily dislodged glass-adherent cells from lesions had surface receptors for the Fc portion of immunoglobulin G and for the third component of complement. Coated red blood cells were readily phagocytized, but noncoated cells were not. Acid lipase activity was demonstrated in the Fc-receptor-positive cells. These cells were also devoid of ultrastructural features of smooth muscle. Among the cells growing or migrating out of explants, a population of large round foam cells possessed all of the macrophage features found in the glass-adherent cells from lesions and lacked ultrastructural characteristics of smooth muscle. Fusiform lipid vacuolated cells also grew out of the explants but did not exhibit surface receptors, failed to phagocytize coated or noncoated erythrocytes and did not stain for acid lipase activity; these cells showed distinctive morphologic features of smooth muscle. In histologic sections of nearby lesions foam cells that showed macrophage characteristics, ie, acid lipase activity and the presence of lysozymelike antigen, lacked ultrastructural smooth muscle features. Smooth muscle cells in lesion sections often contained lipid but demonstrated no lysozyme or acid lipase activity. The occurrence of a population of cells with several functional and structural features of macrophages among the lipid-laden cells of experimental diet-induced arterial lesions suggests that some foam cells may be derived from monocytes. An alternative explanation, that metabolically altered autochthonous arterial wall cells assume one or more characteristics of mononuclear phagocytes is less likely, since some of the markers used in these experiments are unrelated. Both explanations deserve further careful study.

Journal ArticleDOI
TL;DR: The serum concentration of IgG-2 appears to provide a marker for predicting the ability to produce antibodies to polysaccharide, but not viral protein, antigens, in patients treated with both radiation and chemotherapy.
Abstract: We measured serum concentrations of immunoglobulin classes and IgG subclasses in 53 patients who had completed treatment for Hodgkin's disease and in 10 healthy adults. We wished to determine the relation of these classes and subclasses to the subjects' antibody responses to bacterial polysaccharide and viral protein antigens. Mean levels of the IgG-2 subclass were significantly lower in patients treated with both radiation and chemotherapy than in controls (P<0.05). The level of IgG-2 before immunization correlated directly with the mean antibody response both to 11 pneumococcal antigens (r = 0.71, P<0.001) and to the Haemophilus influenzae Type b antigen (r = 0.40, P<0.01). The correlation between IgG-2 concentration and pneumococcal antibody response was also significant in the 10 healthy adults (r = 0.70, P<0.05). The levels of no immunoglobulin class or subclass correlated significantly with antibody responses to influenza A/Victoria/75 and A/New Jersey/76 hemagglutinins, both of which are p...

Journal ArticleDOI
TL;DR: Delta appears to be a marker of a transmissible pathogenic agent, either an HBV variant or another agent that requires the helper functions of HBV, that is defective and interferes with HBV replication.
Abstract: Inoculation of hepatitis B surface antigen (HBsAg)-positive sera from patients with chronic liver disease and intrahepatic delta (delta) into chimpanzees susceptible to infection with hepatitis B virus (HBV) resulted in type B hepatitis and delta markers (delta antigen and antibody to delta) in recipient animals. A dilution (10(-8)) of serum induced type B hepatitis without delta markers in another HBV-susceptible animal. HBV infection and delta markers did not develop in animals with preexisting titers of antibody of HBsAg. In chimpanzees with circulating HBsAg at the time of inoculation, synthesis of delta occurred earlier and its extent and duration were greater than in animals previously unexposed to HBV; coincident with synthesis of delta, hepatitis occurred in chronic HBsAg carriers, and synthesis of preexisting HBV gene products (HBsAg and hepatitis B core antigen) was diminished. Delta appears to be a marker of a transmissible pathogenic agent, either an HBV variant or another agent that requires the helper functions of HBV, that is defective and interferes with HBV replication.

Journal ArticleDOI
TL;DR: There is loss of peripheral suppressor cells in many patients with active MS, suggesting that immunoregulatory abnormalities contribute to the pathogenesis of the disease.
Abstract: To determine whether abnormalities of immunoregulatory T cells are associated with multiple sclerosis (MS), we characterized peripheral lymphocytes in 33 patients with untreated MS and compared them with 42 normal persons and 29 age-matched control subjects who had other neurologic diseases. For this analysis, we used monoclonal antibodies to the surface antigens of helper (T4) and suppressor (T5) T-cell subsets and to a common T-cell antigen (T3). In contract to normal persons and the controls with other neurologic diseases, the patients with MS had a reduced percentage of T3-positive (T3+) cells (P less than 0.05). More importantly, there was a selective decrease in T5-positive (T5+) cells in 11 of 15 patients with active MS, but in only one of 18 patients with inactive MS and in none of the normal persons or controls with neurologic disease (P less than 0.00001). Serial analysis of five patients with MS showed a correlation between the absence of the T5+ subset and disease activity. Thus, there is loss of peripheral suppressor cells in many patients with active MS, suggesting that immunoregulatory abnormalities contribute to the pathogenesis of the disease.

Journal ArticleDOI
TL;DR: It is concluded that the CSP reaction can result from the cross-linking of Pb44 and that it has the characteristics of a capping reaction followed by the shedding of the immune complexes.
Abstract: Monoclonal antibodies (IG1, k) directed against a surface component of Plasmodium berghei sporozoites (Pb-44) confer complete protection to mice against a lethal inoculum of parasites. The degree of protection is a function of the number of parasites used in the challenge and of the antibody concentration in serum. Passive transfer of 10 micrograms of antibody per mouse abolished or profoundly diminished the infectivity of 10(3) sporozoites, but much higher amounts of antibody were required for complete protection against challenge with 10(4) parasites. Fab fragments of the monoclonal antibodies were as effective as the intact antibodies in mediating protection as determined by the neutralizing assay. This observation suggests that the antibodies interfere with a parasite function necessary for its infectivity, such as, for example, the ability to penetrate into the target cell or to multiply in the hepatocytes. When sporozoites are incubated with the intact monoclonal antibodies at 37 degrees C, a long filament appears at its posterior end (circumsporzoite precipitation [CSP] reaction). Fab fragments are ineffective at high concentrations. However, if after treatment with Fab, the sporozoites are incubated with rabbit antibodies to mouse k-chains, a strong CSP reaction is observed. We conclude that the CSP reaction can result from the cross-linking of Pb44 and that it has the characteristics of a capping reaction followed by the shedding of the immune complexes.

Journal Article
TL;DR: Peripheral blood lymphocytes from 15 patients with chronic lymphocytic leukemia (CLL), four patients with lymphosarcoma cell leukemia (LCL), six patients with hairy cell leukemia, and three patients with a monoclonal gammopathy were tested for reactivity with the anti-T cell monoconal antibody, T101, to demonstrate the existence of two major subtypes of CLL that have phenotypes sIg+ and T101+ and sI
Abstract: Peripheral blood lymphocytes from 15 patients with chronic lymphocytic leukemia (CLL), four patients with lymphosarcoma cell leukemia (LCL), four patients with hairy cell leukemia, and three patients with a monoclonal gammopathy (two with IgM, one with IgA) were tested for reactivity with the anti-T cell monoclonal antibody, T101. By immunofluorescent staining, all of the patients had circulating monoclonal surface Ig+ (sIg+) lymphocytes except for three CLL patients whose leukemia cells were sIg-. The leukemia cells of all of the sIg+ CLL cases were reactive with T101 antibody by indirect immunofluorescence; however, the abnormal cells in all of the remaining cases were unreactive. Reactivity of sIg+ CLL cells with T101 was confirmed by a radioactive binding assay, absorption analysis, and complement-dependent cytotoxicity. Moreover, a 65,000-dalton protein (T65), similar to that found on T cells, was precipitated by T101 antibody from the surface of sIg+ CLL cells. The fluorescent staining of sIg+ CLL cells by T101 antibody was weak as was the staining of the sIg. This was in contrast to the LCL cells, which had intense staining sIg and absence of staining with T101 antibody. These data demonstrate the existence of two major subtypes of CLL that have phenotypes sIg+ and T101+ and sIg-T101-. The implication of the finding of dual T and B markers on the major type of CLL, but not other B cell malignancies is discussed.

Journal Article
TL;DR: Preliminary evidence for the lack of clinical toxicity of a monoclonal antibody is provided and circulating blocking antigens as a significant obstacle to serotherapy are identified.
Abstract: A preliminary serotherapeutic trial was undertaken with a monoclonal antibody designated antibody 89 (Ab 89) directed against a lymphoma-associated antigen. In vitro studies demonstrated that Ab 89 could mediate complement-dependent lysis and macrophage adherence but not antibody-dependent cell-mediated cytotoxicity. To evaluate toxicity and therapeutic efficacy, two courses of Ab 89 were administered to a patient with an Ab 89-reactive tumor. Transient decreases in the number of circulating tumor cells and the appearance of circulating dead cells were noted with the infusion of Ab 89. Following administration of 150 mg or more of Ab 89, small amounts of antibody could be demonstrated on circulating tumor cells at a time when no free antibody was found in the serum. The inability to deliver a significant amount of Ab 89 to tumor cells in vivo is thought to be secondary to a circulating tumor antigen. Following each infusion, the amount of this blocking antigen decreased but could not be entirely cleared from the serum. This study provides preliminary evidence for the lack of clinical toxicity of a monoclonal antibody and identifies circulating blocking antigens as a significant obstacle to serotherapy.

Journal ArticleDOI
TL;DR: An indirect immunofluorescence test for detection of serum antibodies specific for nephropathia epidemica (NE) has been developed with use of acetone-fixed cryostat sections of the lungs of bank voles that had been trapped from the NE-endemic area in Finland as antigen.
Abstract: An indirect immunofluorescence test for detection of serum antibodies specific for nephropathia epidemica (NE) has been developed with use of acetone-fixed cryostat sections of the lungs of bank voles (Clethrionomys glareolus) that had been trapped from the NE-endemic area in Finland as antigen. NE antigen was detected as distinct fluorescence in the cytoplasm of alveolar and macrophage-like cells. The 16 patients studied included typical cases from an endemic area, cases from a family outbreak, and cases in a laboratory staff which had had close contact with infected bank voles. Antibodies reacting with antigen in the lung sections developed in all of the patients, but they were not found in the preimmune sera of the patients, in the sera of patients with other renal diseases, or in the sera of healthy individuals, with the exception of a member of the laboratory staff who had lived in the endemic area for 20 years. No specific IgM antibodies to NE could be detected. The rise in titer of antibodies to NE was characteristically prolonged, and elevated antibody levels persisted for many years.

Journal ArticleDOI
TL;DR: A small RNA was temporally associated with delta antigen in the serum of infected chimpanzees and copurified with the delta-antigen-associated particles, smaller than the genomes of known RNA viruses but larger than the viroids of higher plants.
Abstract: The hepatitis B virus-associated beta antigen was found in the serum of experimentally infected chimpanzee as an internal component of a discrete subpopulation of hepatitis B surface antigen (HBsAg) particles. The 35- to 37-nm particles banded in CsCl at 1.24-1.25 g/cm3 and sedimented with a mobility intermediate between that of the hepatitis B virion and that of the 22-nm form of HBsAg. The particles contained only indistinct internal structure by electron microscopy and were not unique to delta agent infection, similar particles without delta-antigen activity being observed in the preinfection serum of HBsAg carrier chimpanzees. A small RNA (Mr, 5 X 10(5)) was temporally associated with delta antigen in the serum of infected chimpanzees and copurified with the delta-antigen-associated particles. This RNA is smaller than the genomes of known RNA viruses but larger than the viroids of higher plants.

Journal ArticleDOI
TL;DR: It appears that intragastric administration of soluble or particulate antigens in mice may lead to the concurrent induction of salivary antibodies and systemic suppression.
Abstract: Diminished systemic immune reaction after ingestion of antigen has been reported in several animal models. Conversely, it has been reported recently that oral immunization may lead to the production of secretory antibodies. To determine whether these events could occur concurrently, CBA/J mice were immunized intragastrically with varying doses of ovalbumin (OVA) and Streptococcus mutans. After 7 d, the animals were challenged systemically with antigen in complete adjuvant and 8 d later serum and saliva taken, and the draining lymph nodes assayed for a proliferative response. Intragastric doses of 1 mg OVA or 10(9) S. mutans led to significant suppression of the proliferative response, and intragastric doses of 10 mg OVA or 2.5 X 10(9) S. mutans led to the production of detectable salivary antibodies using hemagglutination. Serum antibodies were not detected after intragastric administration of OVA or S. mutans. Suppression of the proliferative response could be detected from 2-60 d after intragastric administration of OVA, and 2-21 d after S. mutans. Prior intragastric immunization with heterologous antigens did not suppress the response to OVA or S. mutans. Transfer of 40 X 10(6) mesenteric lymph node cells from mice given 20 mg OVA or 10(9) S. mutans led to suppression of the proliferative response in syngeneic recipients. Salivary antibodies wer removed by absorption with anti-IgA, but not anti-IgG or IgM, indicating that they were of the IgA class. It appears that intragastric administration of soluble or particulate antigens in mice may lead to the concurrent induction of salivary antibodies and systemic suppression.

Journal ArticleDOI
TL;DR: Investigating the immunohistologic architecture of follicular centroblastic/centrocytic lymphoma showed a more or less close similarity to the organization of secondary follicles, which confirmed that this lymphoma was composed of a neoplastic T zone and a non-malignant B zone.
Abstract: Hoping to improve the systems for identifying and classifying normal and malignant lymphoid subpopulations, frozen and paraffin sections of nonmalignant lymphoid tissue and of malignant lymphomas were immunostained for surface (S) and cytoplasmic antigens using the peroxidase-antiperoxidase method. Primary follicle cells and follicle mantle cells known to be part of the recirculating B-cell pool were found to be constantly Ia and C3 receptor (C3R) positive, mostly SIgM and SIgD positive and cytoplasmic immunoglobulin (CIg) negative. The light zone of germinal centers (GC), which is rich in centrocytes, contained a large number of T cells and showed the well-known intercellular Ig network pattern; the dark zone, containing densely packed centroblasts, was usually free of T cells, but was bordered ay a mantle-like accumulation of T cells. Usually only some of the GC cells were definitely positive for SIg and CIg of different classes. All cells reacted positively for Ia and C3R. In areas described by other a...

Journal ArticleDOI
TL;DR: The 94,000-dalton SV40 large T antigen may exist as immunologically distinguishable subclasses, and the nonviral T antigens of five mammalian species share at least one antigenic determinant.
Abstract: We have isolated three clones of hybrid cells which synthesize antibodies specific for determinants on simian virus 40 (SV40) T antigens. Mouse myeloma NS1 cells were fused with spleen cells from mice that had been immunized with SV40-transformed mouse cells. Hybrid cells were selected in HAT medium and cloned in soft agar. We used an enzyme-linked immunosorbent assay for detection and quantification of mouse antibodies against SV40 T antigens. Monoclonal antibodies from 3 of the 24 clones that scored as positive in the enzyme-linked immunosorbent assay were verified by immunoprecipitation to be specific for SV40 T antigens. Two clones (7 and 412) produced antibodies that recognized denaturation-sensitive antigenic determinants unique to large T antigen. Antibodies from clone 7 appeared to have a low affinity for large T antigen. Antibodies from clone 412 had a higher affinity for large T antigen but did not recognize a subclass of large T antigen that was recognized by tumor serum. Antibodies of the third clone, clone 122, recognized a denaturation-stable antigenic determinant of the 53,000-dalton mouse nonviral T antigen in SV40-transformed cells. Antibodies from clone 122 also recognized similar (51,000- to 56,000-dalton) nonviral T antigens in SV40-transormed or lytically infected cells from five mammalian species and in four uninfected mouse lines. From these observations, we have concluded that (i) the 94,000-dalton SV40 large T antigen may exist as immunologically distinguishable subclasses, and (ii) the nonviral T antigens of five mammalian species share at least one antigenic determinant.

Journal ArticleDOI
TL;DR: Using an immunoperoxidase method, factor VIII-related antigen was localized in vascular endothelial cells and may be used to confirm the vascular nature of a variety of hyperplastic and neoplastic lesions of skin, soft tissues, and other locations.
Abstract: Using an immunoperoxidase method, factor VIII-related antigen was localized in vascular endothelial cells. This method provides a marker for endothelial cells at the tissue level and may be used to confirm the vascular nature of a variety of hyperplastic and neoplastic lesions of skin, soft tissues, and other locations.

Journal ArticleDOI
TL;DR: It was noted that the distribution of DR antigens in the hydralazine-SLE patients was significantly different from that in the group with idiopathic SLE, which supports the view that the syndromes are separate entities.