Showing papers on "Antigen published in 1973"
TL;DR: The ACIF test was used as a tool to trace the Epstein‐Barr virus genome at the cellular level to study the complementfixing antigens of human lymphoblastoid cell lines.
Abstract: Anti-complement immunofluorescence (ACIF) was used to study the complementfixing antigens of human lymphoblastoid cell lines. These cell lines carry the Epstein-Barr virus (EBV) genome although only producer cultures synthetize EBV-specific antigens (virus capsid antigen, VCA and early antigen, EA) detectable by direct and indirect immunofluorescence, usually in less than 5% of the cells. The ACIF test revealed an antigen localized in the nucleus of the lymphoblastoid cells. In contrast to EA and VCA, this antigen was present in over 90% of the cells of both producer and non-producer cultures. The antigen was shown to be specific for EBV by comparing the reactions of 52 sera in the ACIF test. Sera giving the nuclear reaction contained antibodies to VCA, EA or antigens detectable by complement fixation tests on cell extracts, but sera without EBV antibodies failed to give the reaction. Weak, equivocal or discordant reactions occurred with six sera with low titres in VCA, EA or complement fixation tests. Cell lines derived by transformation of human and primate lymphocytes by EBV gave the nuclear reaction. Control cells with no known association with EBV were non-reactive. These included foetal lymphocytes transformed by phytohaemagglutinin, cell lines derived from breast cancer, glioma, normal glia, pleuritis maligna and myeloma, and two marmoset lymphoid lines carrying Herpesvirus saimiri (HVS). In preliminary experiments, the ACIF test was used as a tool to trace the EBV genome at the cellular level. Cells from two Burkitt lymphoma biopsies, one tested after biopsy and one after passaging in nude mice, contained an EBV-specific antigen. Three clones of cells derived from hybrids of mouse somatic cells and a human lymphoblastoid cell line also contained such an antigen, but the number of reactive cells varied from clone to clone. A fourth clone was non-reactive.
1,632 citations
TL;DR: It is established that exogenous AHF procoagulant activity is not inactivated by the tissue culture system.
Abstract: Antihemophilic factor (AHF, Factor VIII) antigen has been demonstrated in cultured human endothelial cells by immunofluorescence studies using monospecific rabbit antibody to human AHF. Control studies with cultured human smooth muscle cells and human fibroblasts were negative. By radioimmunoassay it was demonstrated that cultured human endothelial cells contain AHF antigen which is released into the culture medium. Cultured smooth muscle cells and fibroblasts did not have this property. Cultured endothelial cells incorporated radioactive amino acids into high molecular weight, AHF antigen-rich protein fractions prepared from the culture media, 7% of the radioactive amino acid counts incorporated into this material were precipitated by globulin prepared from rabbit anti-AHF whereas normal rabbit globulin precipitated only 1.5% of the counts. Although cultured endothelial cells actively synthesize AHF antigen, AHF procoagulant activity was not detected in the culture medium. Studies seeking a basis for the lack of procoagulant activity have not clarified this deficiency, but they have established that exogenous AHF procoagulant activity is not inactivated by the tissue culture system.
1,242 citations
TL;DR: The data demonstrate that efficient presentation of macrophage-associated antigen to the lymphocyte requires identity between macrophages and lymphocyte at some portion of the major histocompatibility complex.
Abstract: Antigen activation of DNA synthesis in immune thymus-derived lymphocytes of guinea pigs requires the cooperation of macrophages and lymphocytes. We have investigated the role of histocompatibility determinants in this macrophage-lymphocyte interaction using cells from inbred strain 2 and 13 guinea pigs. The data demonstrate that efficient presentation of macrophage-associated antigen to the lymphocyte requires identity between macrophage and lymphocyte at some portion of the major histocompatibility complex. The failure of allogeneic macrophages to effectively initiate immune lymphocyte proliferation was not the result of the presence of an inhibitor of blastogenesis released in mixtures of allogeneic cells, peculiarities of the antigen or lymphoid cells employed, nor differing kinetics of activation by allogeneic macrophages. In addition, data were presented that demonstrated that alloantisera inhibit lymphocyte DNA synthesis by functional interference with macrophage-lymphocyte interaction.
939 citations
TL;DR: Mouse hearts were transplanted heterotopically as primarily vascularized grafts to provide combinations in which there was histoincompatibility with respect to antigens whose specificities are determined by genes at the H-2D region only and there was a close relationship between the survival times of allografts of hearts and skin.
Abstract: SUMMARYMouse hearts were transplanted heterotopically as primarily vascularized grafts. Donors and recipients were selected to provide combinations in which there was histoincompatibility with respect to antigens whose specificities are determined by genes at the H-2D region only (B10.BR → B6AF1), a
809 citations
TL;DR: Spherical 27-nanometer particles were visualized in stools obtained from hepatitis A patients in the acute phase of the disease and suggest that it is the etiologic agent of hepatitis A.
Abstract: Spherical 27-nanometer particles were visualized in stools obtained from hepatitis A patients in the acute phase of the disease. The particle was serologically specific for this disease, and every hepatitis A patient tested demonstrated a serologic response to this antigen. The findings suggest that it is the etiologic agent of hepatitis A.
774 citations
TL;DR: DNA polymerase activity was detected in each of eight preparations of concentrated human hepatitis B antigen (HBAg) rich in Dane particles prepared by high-speed centrifugation of antigen-positive human plasma and in none of seven control preparations prepared in the same way from HBAg-negative plasma.
Abstract: DNA polymerase activity was detected in each of eight preparations of concentrated human hepatitis B antigen (HBAg) rich in Dane particles prepared by high-speed centrifugation of antigen-positive human plasma and in none of seven control preparations prepared in the same way from HBAg-negative plasma. The incorporation of (3)H-thymidine-methyl-5'-triphosphate into DNA was dependent on four deoxyribonucleoside triphosphates and MgCl(2). Treatment of the concentrated HBAg preparations with the nonionic detergent Nonidet P-40 (NP40) more than doubled the enzyme activity. Fractionation of the concentrated HBAg preparation in sucrose density gradients after treatment with NP40 revealed that the enzyme activity appeared within the density range of Dane core antigen but at a slightly higher density than the average for core antigen. The only particles observed by electron microscopy in this region of the gradient were typical 28-nm cores, suggesting that the DNA polymerase activity was associated with a subpopulation of cores. No DNA polymerase activity was found in purified 20-nm HBAg particles. The DNA product of the reaction remained associated with the 110S core and was not susceptible to DNase digestion when associated with the core. Inhibition of the reaction by actinomycin D and daunomycin suggested that the reaction was dependent on a DNA template associated with the core.
709 citations
TL;DR: Primary rat embryo and baby rat kidney cells have been transformed by human adenovirus 5 DNA and the efficiency was approximately 1 transformed focus/μg DNA.
693 citations
TL;DR: It is concluded that antigen recognition by the T lymphocyte is a complex multicellular event involving more than simple antigen binding to a specific lymphocyte receptor.
Abstract: A number of recent studies have suggested that the main functional role of the product of the immune response (Ir) genes is in the process of antigen recognition by the T lymphocyte. The observation in the accompanying report that the interaction of macrophage-associated antigen with immune T lymphocytes requires that both cells share histocompatibility antigens raised the question as to whether the macrophage played a role in the genetic control of the immune response or even if the macrophage were the primary cell in which the product of the Ir gene is expressed. In the current study, parental macrophages were pulsed with an antigen, the response to which is controlled by an Ir gene lacking in that parent; these macrophages were then mixed with T cells derived from the (nonresponder x responder)F1 and the resultant stimulation was measured. No stimulation was seen when column-purified F1 lymph node lymphocytes were mixed with antigen-pulsed macrophages from the nonresponder parent. However, when the highly reactive peritoneal exudate lymphocyte population was used as the indicator cells, parental macrophages pulsed with an antigen whose Ir gene they lacked were capable of initiating F1 T-cell proliferation. The magnitude of stimulation was approximately 1/10 that seen when macrophages from either the responder parent or the F1 were used. In order to explain this observation, we hypothesize that antigen recognition sites on the T lymphocyte are physically related to a macrophage-binding site and both are linked to the serologically determined histocompatibility antigens. Thus, parental macrophages pulsed with an antigen, whose Ir gene they lack, activate F1 cells poorly because the recognition sites for the antigen are physically related to the macrophage-binding site of the responder parent while the main contacts between the cells are at the nonresponder binding sites. Experiments performed with alloantisera lend support to this hypothesis. Thus, when parental macrophages are pulsed with any antigen and added to F1 T cells, an alloantiserum directed against parental histocompatibility antigens reacts with both the lymphocyte and the macrophage and thereby inhibits macrophage-lymphocyte interaction and abolishes antigen-induced lymphocyte transformation. When the alloantisera are directed at determinants present solely on the T lymphocyte, they only inhibit the recognition of antigens controlled by the Ir gene linked to the histocompatibility antigen against which they are directed. We conclude from these studies that antigen recognition by the T lymphocyte is a complex multicellular event involving more than simple antigen binding to a specific lymphocyte receptor.
626 citations
TL;DR: This chapter summarizes the data presented in two reviews of experimental acute and chronic immune complex disease produced by nonliving antigens and discusses in detail more recent studies.
Abstract: Publisher Summary No experimental model has provided greater insight into the mechanism of immune complex disease than the experimental serum sickness. The morphological, immunohistological, and serological features of the laboratory models have provided a basis for understanding the pathogenic mechanisms responsible for human glomerulonephritis, vasculitis, and a variety of systemic connective tissue diseases. The subject of experimental acute and chronic immune complex disease produced by nonliving antigens has received extensive review in this series. This chapter summarizes the data presented in these two reviews and discusses in detail more recent studies. Experiments to study acute immune complex disease (serum sickness) have been performed in rabbits almost exclusively. Experimental chronic immune complex disease has proved to be a most useful model in understanding human glomerulonephritis. When injected daily with heterologous serum protein antigens, rabbits with strong antibody responses develop chronic membranous glomerulonephritis in about 5 weeks.
539 citations
TL;DR: The permanent presence of tumour‐specific antigen (TSA) in this carcinoma cell line suggests that the TSA is a genetically determined characteristic of T24 cells.
Abstract: A cell line derived from human urinary bladder carcinoma, designated T24, was established in vitro. The growth of T24 cells in tissue culture was characterized by a disorderly pattern of growth in one or more layers and by mixed epithelioid-fibroblastoid morphology. The generation time of T24 cells was 19 h. The cells had a hypotetraploid stemline with marker chromosomes. The malignant character of the line was verified by inoculation of cell suspension into hamster cheek pouch. The presence of tumour-specific antigen (TSA) in T24 cells was demonstrated by a micromodification of the cytotoxicity test with autochthonous leukocytes and serum from the donor of the tumour. The TSA was also well detectable by the reaction with allogeneic leukocytes from tumour-bearing patients and persisted during a 30-month culture period. The permanent presence of TSA in this carcinoma cell line suggests that the TSA is a genetically determined characteristic of T24 cells.
522 citations
TL;DR: Investigation of the pathogenesis of acute herpetic infection in the nervous system of mice indicated that neurons were found to produce morphologically complete virions, but supporting cells replicated principally nucleocapsids, considered to offer strong support for centripetal transport in axons.
Abstract: The pathogenesis of acute herpetic infection in the nervous system has been studied following rear footpad inoculation of mice. Viral assays performed on appropriate tissues at various time intervals indicated that the infection progressed sequentially from peripheral to the central nervous system, with infectious virus reaching the sacrosciatic spinal ganglia in 20 to 24 hr. The infection also progressed to ganglia in mice given high levels of anti-viral antibody. Immunofluorescent techniques demonstrated that both neurons and supporting cells produced virus-specific antigens. By electron microscopy, neurons were found to produce morphologically complete virions, but supporting cells replicated principally nucleocapsids. These results are discussed in the context of possible mechanisms by which herpes simplex virus might travel in nerve trunks. They are considered to offer strong support for centripetal transport in axons.
TL;DR: The demonstration of fluorescence within the cytoplasm of endothelial cells suggests that these cells synthesize proteins that have AHF antigens, which is in line with previous reports on antihemophilic factor.
Abstract: The tissue localization of antihemophilic factor (AHF, Factor VIII) has been determined by immunofluorescent studies using monospecific rabbit antibody to human AHF. Specific staining demonstrating AHF antigens has been identified in endothelial cells of a wide range of human tissues. The staining pattern was observed in endothelial cells of arteries, capillaries, and veins as well as the cells lining hepatic and splenic sinusoids. Specific fluorescence was limited to these endothelial cells in sections of kidney, liver, spleen, lymph node, cardiac and smooth muscle, thyroid, umbilical cord, and skin. Absorption studies established that the staining was specific for cells in which there were proteins that had AHF antigens. The demonstration of fluorescence within the cytoplasm of endothelial cells suggests that these cells synthesize proteins that have AHF antigens.
TL;DR: The distribution of HL-A antigens, and the incidence of lymphocytotoxic and tissue antibodies in the two patient groups was not different from that in the control population and specificity W15 was present in significantly higher frequency in the insulin-dependent diabetic patients.
Abstract: Diabetes mellitus is a genetically determined disorder of metabolism in which inherited susceptibility plays an important part. We studied the distribution of HL-A antigens, and theincidence of lymphocytotoxic and tissue antibodies in seventy-one adult diabetic patients—fifty insulin-dependent and twenty-one insulin-independent. Specificity W15 was present in significantlyhigher frequency in the insulin-dependent diabetic patients than either in the control group (P = 0.0005) or in the insulin-independent diabetic patient group (P
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TL;DR: Furthermore, PEG has been used at lower concentrations in order to precipitate soluble antigen-antibody complexes in conditions at which free antigen or free antibody would be soluble.
Abstract: Furthermore, PEG has been used at lower concentrations in order to precipitate soluble antigen-antibody complexes in conditions at which free antigen or free antibody would be soluble. This second method could be applied to larger antigens such as IgG or thyroglobulin.
TL;DR: Through the use of absorbed idiotypic antisera prepared against single isolated monoclonal IgM anti-γ-globulins, partial cross-idiotypic specificity was demonstrated, indicating basic similarities between proteins of a given activity even in unrelated individuals.
Abstract: Through the use of absorbed idiotypic antisera prepared against single isolated monoclonal IgM anti-γ-globulins, partial cross-idiotypic specificity was demonstrated with other IgM anti-γ-globulins. Such antisera classified these proteins into at least three groups. The major group which included 60% of the anti-γ-globulins was particularly homogeneous. The anti-γ-globulin specific antigens were detected best in hemagglutination and hemagglutination inhibition systems. They were not found in monoclonal IgM proteins that lacked anti-γ-globulin activity although related antigens were detected at low concentrations in pooled immunoglobulin preparations as well as in heterogeneous anti-Rh antibodies.
Several lines of evidence were obtained indicating that the antibody combining site was involved in the specific determinants. Attempts were made to analyze the fine specificity of each anti-γ-globulin for the Fc fragment of different subclasses of human immunoglobulins as well as those of other species. Differences were observed but these were not readily related to the cross-specificity antigens.
The anti-γ-globulin specific antigens were very analogous to those previously described for monoclonal IgM cold agglutinins. Although each protein could be distinguished from all the others on the basis of individual idiotypic antigens, the antigens common to the specific groups of proteins with each of these activities were prominent and readily detected with multiple antisera. The results indicate basic similarities between proteins of a given activity even in unrelated individuals.
TL;DR: These studies demonstrate that GLT-primed T cells of CAF1 donors can provide for responder BALB/c, but not for nonresponder A/J, the required stimulus for the anti-DNP responses of DNP-specific B cells of these respective parental strains to the DNP conjugate of GLT.
Abstract: Several experimental approaches, designed specifically to circumvent the possible contribution of a complicating "allogeneic effect," have been successfully used to answer the question of physiologic cooperative interactions between histoincompatible T and B lymphocytes in antibody responses to hapten-protein conjugates. This was accomplished for in vivo cell transfer studies by using an F1 hybrid host as the recipient of irradiated, carrier-primed T lymphocytes from one parent and 2,4-dinitrophenyl (DNP)-primed B lymphocytes from the opposite strain. Under these conditions, very good T-B cell cooperative interactions were observed to occur between T and B lymphocyte populations derived from syngeneic donors, whereas no cooperative response was obtained when T cells were derived from one parental strain and B cells from the other. Corroborative experiments were performed in a totally in vitro system in which DNP-primed B cells developed good secondary anti-DNP antibody responses in vitro to soluble DNP-keyhole limpet hemocyanin (KLH) when cultured in the presence of irradiated KLH-primed T cells derived from syngenic donors but not from allogeneic donors.
The failure of histoincompatible T and B lymphocytes to effect physiologic cooperative interactions has important implications for our understanding of how such interactions normally occur. The possibility that these results reflect the existence of a "block" of some sort to cell-cell interaction by virtue of the presence of a foreign major histocompatibility antigen on the surface of either cell has been definitively ruled out in the present studies. These observations demonstrate that the gene(s) that conditions the capability for physiologic T-B cell cooperation must be shared in common by the respective cell types, and suggest, furthermore, that this gene (or genes) belongs to the major histocompatibility system of the mouse. These findings, together with other relevant phenomena described previously, have led us to postulate that there exists on the B lymphocyte surface an "acceptor" molecule either for the putative active T cell product or for the T cell itself. The important genetic considerations and the possible sequence of events surrounding the actual T-B cell interaction implied by these postulates are discussed in detail.
TL;DR: A new slide-agglutination method was developed for the serological typing of pneumococci, where type-specific antibodies were bound to stabilised, protein-A containing staphylococci through theri Fc fragments.
Abstract: Summary
A new slide-agglutination method was developed for the serological typing of pneumococci. Type-specific antibodies were bound to stabilised, protein-A containing staphylococci through theri Fc fragments. The combining sites of the antibodies remained available to the corresponding type-specific antigen; when pneumococci were mixed with a suspension of the stabilised staphylococci coated with homologous antibody, strong agglutination occurred rapidly. Eighty-nine pneumococcal strains were typed by this agglutination method. The results obtained were in complete agreement with those of typing by Neufeld's capsule-“ swelling” method.
TL;DR: In 15 patients, antibodies to core appeared in acute viral hepatitis, type B, twelve to twenty weeks after exposure, usually during antigenaemia and well before the appearance of anti-HBAg, and anti-core antibodies were found in all chronic HBAg carriers tested.
TL;DR: It is concluded that the presence of Liver cell dysplasia identifies a group of patients with a high risk of liver cell carcinoma and that they should be followed up by serial alpha-fetoprotein estimations.
Abstract: Liver cell dysplasia is defined as cellular enlargement, nuclear pleomorphism, and multinucleation of liver cells occurring in groups or occupying whole cirrhotic nodules. The prevalence, natural history, and relationship to the Australia or hepatitis-associated antigen (HAA) have been studied in 552 Ugandan African patients with normal, cirrhotic, and cancerous livers. Liver cell dysplasia was found in only two of 200 (1%) patients with normal livers, in three of 43 (6·9%) of patients with normal livers bearing primary liver cell carcinoma, 35 of 175 (20·3%) patients with cirrhosis, and 80 of 124 (64·5%) of patients with cirrhosis and primary liver cell carcinoma. Cirrhotic patients without dysplasia were, on average, ten years younger than those with dysplasia and the latter were on average six years younger than those with cirrhosis and carcinoma. Liver cell dysplasia occurred more frequently in males than in females. It was found in all but one instance in macronodular or mixed forms of cirrhosis only. There was a strong relationship between dysplasia and the presence of HAA in 104 patients that suggests a possible carcinogenic mechanism for the longincubation (serum or B) hepatitis virus in liver cell carcinoma. It is concluded that the presence of liver cell dysplasia identifies a group of patients with a high risk of liver cell carcinoma and that they should be followed up by serial alpha-fetoprotein estimations.
TL;DR: Syngeneic antisera have been produced in mouse strain 129/Sv-CP males against the primitive cells of teratocarcinoma and reveal that teratoma cells possess cell-surface antigens in common with normal cleavage-stage embryos.
Abstract: Syngeneic antisera have been produced in mouse strain 129/Sv-CP males against the primitive cells of teratocarcinoma. These sera react specifically with the primitive cells and are negative on various types of differentiated teratoma cells derived from the same original tumor. They are negative on all other mouse cells tested, with the exception of male germ cells and cleavage-stage embryos. Thus, teratoma cells possess cell-surface antigens in common with normal cleavage-stage embryos.
TL;DR: The “protective” level of serum anti-type b antibodies, estimated by two methods, was achieved by immunization of infants, which suggests that this procedure may confer protective immunity.
Abstract: Extract: Haemophilus influenzae type b antibodies were measured quantitatively in normal and immunized humans and in commercially available pooled immunoglobulin. A “protective” serum level was estimated to be 0.06 to 0.1 $mUg antibody/ml based upon the anti-type b concentration in normal adult sera and pooled immunoglobulin. An age-related difference characterized the adult and infant serum antibody response to injection of the purified type b capsular polysaccharide. The adults responded with higher and sustained antibody levels than the infants and children. An immunized infant reacted with type b antibody formation after nasopharyngeal carriage of H. influenzae type b and two infants reacted with type b antibodies after enteric carriage of Escherichia coli with a cross-reacting antigen. Speculation: Qualitative and quantitative differences characterize the adult versus the infant re-response to the capsular polysaccharide of H. influenzae type b. This age-related difference in the serum anti-type b antibody response may be due to the development of differentiated cells induced by whole bacteria, either as H. influenzae type b or by other organisms with cross-reacting antigens. The “protective” level of serum anti-type b antibodies, estimated by two methods, was achieved by immunization of infants, which suggests that this procedure may confer protective immunity.
TL;DR: The results imply that Epstein-Barr virus is capable of inducing malignant lymphoma in at least one primate species, and additional evidence is required before its oncogenic capacity in this host can be accepted without reservation.
Abstract: Neoplasia resembling human malignant lymphoma, reticulum cell sarcoma type, occurred in cottontop marmosets inoculated with materials containing Epstein-Barr virus. One of four monkeys that received autologous cells transformed in vitro by Epstein-Barr virus developed lymphoma in mesenteric lymph nodes 7.5 months after inoculation. Three of four marmosets inoculated with cell-free Epstein-Barr virus developed lymphoma. The latent period for detectable tumor formation after addition of virus was 31-46 days. Immunosuppressive drugs given with the virus accelerated the course of disease. Nevertheless, malignant lymphoma occurred in an animal given only cell-free virus. Six of eight marmosets inoculated with the virus demonstrated antibodies to the virus. Four marmosets not exposed to the virus, including two that received immunosuppressive drugs, developed neither tumors nor antibodies to Epstein-Barr virus. Virus antigen detectable by immunofluorescence was found in 5% of cells shed from one tumor maintained in organ culture. These results imply that Epstein-Barr virus is capable of inducing malignant lymphoma in at least one primate species. Additional evidence is required before its oncogenic capacity in this host can be accepted without reservation.
TL;DR: Although virus was not recovered from extracts of serially cultured tumor cells, JC virus was rescued when one tumor cell line was fused with permissive cells, and this antigen was antigenically related to SV40 T antigen.
Abstract: Eighty-three percent of hamsters inoculated at birth with JC virus, a human papovavirus isolated from brain tissue of a case of progressive multifocal leukoencephalopathy, developed malignant gliomas within 6 months. Three brain tumors have been serially transplanted as subcutaneous tumors. JC virus was isolated from five of seven tumors tested. Cells from four tumors were cultivated in vitro. These cells contained an intranuclear antigen with the characteristics of a T antigen, and this antigen was antigenically related to SV40 T antigen. Although virus was not recovered from extracts of serially cultured tumor cells, JC virus was rescued when one tumor cell line was fused with permissive cells.
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TL;DR: The envelope glycoprotein of rabies virus was shown to be the antigen responsible for the induction of virus neutralizing (VN) antibody formation and for the protection of animals against subsequent challenge with rabies, which could be explained by the amount of residual glycop protein present in these preparations.
Abstract: The envelope glycoprotein of rabies virus was shown to be the antigen responsible for the induction of virus neutralizing (VN) antibody formation and for the protection of animals against subsequent challenge with rabies virus. Preparation of two other envelope proteins and of the nucleocapsid protein, derived from disrupted virions, induced the formation of only low levels of VN antibody and protection of animals against rabies, which could be explained by the amount of residual glycoprotein present in these preparations. Purified preparations of free viral nucleocapsid, isolated from infected cells, did not induce VN antibody formation, but elicited, in immunized animals, the formation of antibodies demonstrable by complement fixation or fluorescent antibody tests.
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TL;DR: Evidence is presented which emphasizes the striking similarities in properties of MIF and Type II interferon, although it is not possible to determine whether the two mediators are the same or different protein molecules.
Abstract: Further evidence is presented of the coordinate production and similar properties of two mediators, migration inhibitory factor (MIF) and interferon, in the circulation of BCG-infected mice inoculated with specific antigen (Old Tuberculin, OT). In addition, the interferon elicited by OT in BCG-infected mice is shown to be a distinct molecular species of viral inhibitor and is designated “Type II interferon.” The designation “Type I interferon” is used to describe the viral inhibitor produced in BCG-infected or control mice given nonspecific stimuli such as bacterial lipopolysaccharide (LPS) or Newcastle disease virus (NDV). Although Type II interferon possesses the biologic attributes required to classify a viral inhibitor as “interferon,” it, as well as MIF, differs markedly from Type I interferon in stability at pH 2 and at 56°C, range of species specificity, and antigenicity. Antibodies against highly purified L cell interferon induced by NDV (anti-Type I interferon antibodies) neutralize the activity of interferons elicited in mice by nonspecific stimuli such as LPS or NDV. In contrast, the antiviral activity of Type II interferon and the macrophage-inhibitory activity of MIF, elicited by specific antigen in mice with delayed hypersensitivity, are not affected by high concentrations of antibody against Type I interferon. Evidence is presented which emphasizes the striking similarities in properties of MIF and Type II interferon, although it is not possible to determine whether the two mediators are the same or different protein molecules.
TL;DR: It seems possible that there may be a variety of H-2-linked alloantigens expressed preferentially on subclasses of lymphocytes, as reactions with recombinant strains of mice indicate that the cell-surface antigen responsible for this specificity is determined by gene in or to the left of the Ir-1 region of the major histocompatibility complex.
Abstract: Antibodies cytotoxic for only a subpopulation of C57Bl/10 lymph node and spleen cells were detected when rat antiserum against B10.D2 was exhaustively absorbed with B10.A lymphocytes. Antibodies of similar specificity were also detected in B10.A anti-B10.D2 and in B10.A anti-C57Bl/10 alloantisera. Reactions with recombinant strains of mice indicate that the cell-surface antigen(s) responsible for this specificity is determined by gene(s) in or to the left of the Ir-1 region of the major histocompatibility complex. A variety of criteria implicate B cells as the subpopulation of lymphocytes bearing this antigen. In view of these data and the recent report by others of a T-cell alloantigen determined by gene(s) in the major histocompatibility complex, it seems possible that there may be a variety of H-2-linked alloantigens expressed preferentially on subclasses of lymphocytes.
TL;DR: A new system of lymphocyte alloantigens in mice is described and may be of value for definition and characterization of the products of the Ir and MLR (mixed lymphocyte reaction stimulatory) genes associated with the H-2 complex.
Abstract: A new system of lymphocyte alloantigens in mice is described. This Lna (lymph-node antigen) system is associated with the Ir region of the H-2 (histocompatibility-2) gene complex. It has the following distinctive characteristics: (1) The gene or genes controlling these antigens has been mapped in the Ir (immune response) region between H-2K and Ss-Slp. (2) The antigens are most readily detectable on lymph-node cells, although they are also expressed on peripheral blood lymphocytes, splenic lymphocytes, and thymocytes. (3) Cytotoxicity against only about half of lymph-node cells is consistently observed. (4) Cytotoxic antibody titers against these antigens are strikingly high—more than 2000 by 51Cr-release and up to 100,000 in the microcytotoxic test. (5) At least two, probably allelic, forms of the antigen(s) have been defined, one associated with the H-2k haplotype and one with the H-2a haplotype. (6) Antisera against Lna contain multiple antibody specificities that can be fractionated by absorption either with certain recombinants or with other H-2 halotypes that have crossreactive antigens. The antisera against Lna may be of value for definition and characterization of the products of the Ir and MLR (mixed lymphocyte reaction stimulatory) genes associated with the H-2 complex.
TL;DR: A self-consistent map could be constructed which related specific regions of the SV40 genome to the induction of specific antigens in the nondefective Ad2-SV40 hybrids.
Abstract: A series of viable recombinants between adenovirus 2 (Ad2) and simian virus 40 (SV40) (nondefective Ad2-SV40 hybrids) have been isolated. The members of this series (designated Ad2 + ND 1 through Ad2 + ND 5 ) differ from one another in the early SV40-specific antigens and the SV40-specific RNA species which they induce in infected cells. They also contain different amounts of SV40 DNA as shown by RNA-DNA hybridization techniques. We have examined the structure of the DNA molecules from these hybrids, using electron microscope heteroduplex mapping techniques. Each hybrid was found to contain a single segment of SV40 DNA of characteristic size covalently inserted at a unique location in the adenovirus 2 DNA molecule. The SV40 segments of the various hybrids formed an overlapping series with a common end point. When the results of the electron microscopic study were combined with data on antigen induction, it was found that a self-consistent map could be constructed which related specific regions of the SV40 genome to the induction of specific antigens. The order of these early SV40 antigen inducing regions in the SV40 DNA segments contained in the nondefective hybrids is: U antigen, tumor specific transplantation antigen, and T antigen with the U antigen region being nearest the common end point. Images
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TL;DR: The mitogens phytohemagglutinin and concanavalin A stimulate only those mouse lymphocytes which have undergone differentiation within the thymus and thus bear the differentiation antigen θ, and the differential responsiveness of T cells to PHA and Con A may be used to indicate the existence of T cell subsets.
Abstract: The mitogens phytohemagglutinin (PHA) and concanavalin A (Con A) stimulate only those mouse lymphocytes which have undergone differentiation within the thymus and thus bear the differentiation antigen θ. However, not all thymus-derived lymphocytes (T cells) react equally to both mitogens, and the differential responsiveness of T cells to PHA and Con A may be used to indicate the existence of T cell subsets. One subpopulation of T cells exists which demonstrates approximately equal reactivity to both mitogens and bears a relatively high density of θ determinants. Another subpopulation exists which responds mainly to Con A, and bears a relatively reduced density of θ determinants. T cell subsets so delineated also differ in their recirculation patterns, radiation sensitivities, location in peripheral lymphoid tissue, and most importantly, in their function. These differential characteristics may represent the capabilities of T cells in various stages of differentiation within one T cell line. On the other hand, these cells may be representative of two distinct T cell lines and preliminary evidence consistent with this possibility is presented.