Showing papers on "Antigen published in 1984"
Journal Article•
TL;DR: The data suggest that the early stages of mitogen stimulation represent initial sequences of proliferation and not parts of the cell cycle, and immunostaining with monoclonal antibody Ki-67 provides a reliable means of rapidly evaluating the growth fraction of normal and neoplastic human cell populations.
Abstract: The monoclonal antibody Ki-67 detects a nuclear antigen that is present only in proliferating cells. The aim of the present investigation was to clarify whether the Ki-67 nuclear antigen is restricted in its expression to certain phases of the cell cycle. All experiments consistently showed that the Ki-67 nuclear antigen is present in S, G2, and M phase, but is absent in G0. However, the results concerning Ki-67 antigen expression in G1 phase varied: cells passing the early events of mitogen triggered transition from G0 to G1, i.e., G1T and first G1A, lacked the Ki-67 nuclear antigen, whereas G1 cells after mitosis were constantly Ki-67-positive. This result suggests that after mitosis cells might not follow the same metabolic pathways as G0 cells do when entering G1 for the first time. Therefore, we suggest that the early stages of mitogen stimulation represent initial sequences of proliferation and not parts of the cell cycle. Because our data show that the Ki-67 nuclear antigen is present throughout the cell cycle, immunostaining with monoclonal antibody Ki-67 provides a reliable means of rapidly evaluating the growth fraction of normal and neoplastic human cell populations.
4,093 citations
TL;DR: It is concluded that the CD4 antigen is an essential and specific component of the receptor for the causative agent of AIDS.
Abstract: Acquired immune deficiency syndrome (AIDS) is characterized by opportunistic infections and by 'opportunistic neoplasms' (for example, Kaposi's sarcoma). Persistent generalized lymphadenopathy (PGL) is epidemiologically associated with AIDS, especially in male homosexuals. A subset of T lymphocytes positive for the CD4 antigen (also termed T4 antigen), is depleted in AIDS and PGL patients. A retrovirus found in T-cell cultures from these patients is strongly implicated in the aetiology of AIDS because of the high frequency of isolation and the prevalence of specific antibodies in the patients. Here we have detected cell-surface receptors for the AIDS retrovirus (human T-cell leukaemia virus-III (HTLV-III) and lymphadenopathy-associated virus-1 (LAV-1) isolates) by testing the susceptibility of cells to infection with pseudotypes of vesicular stomatitis virus bearing retroviral envelope antigens, and by the formation of multinucleated syncytia on mixing virus-producing cells with receptor-bearing cells. Receptors were present only on cells expressing CD4 antigen; among 155 monoclonal antibodies tested, each of the 14 anti-CD4 antibodies inhibited formation of syncytia and blocked pseudotypes. Productive infection of CD4+ cells with HTLV-III or LAV-1 markedly reduced cell-surface expression of CD4. In contrast, receptors for HTLV-I and HTLV-II were not restricted to CD4+ cells, were not blocked by anti-CD4 antibodies; cells productively infected with HTLV-I and HTLV-II expressed surface CD4. Hence, we conclude that the CD4 antigen is an essential and specific component of the receptor for the causative agent of AIDS.
3,631 citations
TL;DR: Preincubation of T4+ lymphocytes with three individual monoclonal antibodies directed at the T4 glycoprotein blocked cell infection by LAV, strongly support the view that a surface molecule directly involved in cellular functions acts as, or is related to, the receptor for a human retrovirus.
Abstract: Many viruses, including retroviruses, are characterized by their specific cell tropism. Lymphadenopathy-associated virus (LAV) is a human lymphotropic retrovirus isolated from patients with acquired immune deficiency syndrome (AIDS) or related syndromes, that displays selective tropism for a subset of T lymphocytes defined by the expression of a surface glycoprotein of relative molecular mass 62,000 (62K) termed T4 (refs 6-8). This glycoprotein delineates a subset of T lymphocytes with mainly helper/inducer functions, while T lymphocytes of the reciprocal subset express a glycoprotein termed T8, have mainly cytotoxic/suppressor activities, and are unable to replicate LAV. Such a tropism may be controlled at the genomic level by regulatory sequences, as described for the human T-cell leukaemia viruses HTLV-I and -II (refs 2, 3). Alternatively or concomitantly, productive cell infection may be controlled at the membrane level, requiring the interaction of a specific cellular receptor with the virus envelope, as demonstrated recently for Epstein-Barr virus (EBV). Therefore, we have investigated whether the T4 molecule itself is related to the receptor for LAV. We report here that preincubation of T4+ lymphocytes with three individual monoclonal antibodies directed at the T4 glycoprotein blocked cell infection by LAV. This blocking effect was specific, as other monoclonal antibodies--such as antibody to histocompatibility locus antigen (HLA) class II or anti-T-cell natural killer (TNK) target--directed at other surface structures strongly expressed on activated cultured T4+ cells, did not prevent LAV infection. Direct virus neutralization by monoclonal antibodies was also ruled out. These results strongly support the view that a surface molecule directly involved in cellular functions acts as, or is related to, the receptor for a human retrovirus.
2,482 citations
TL;DR: Chimeric genes were constructed that utilized the rearranged and expressed antigen-binding variable region exons from the myeloma cell line S107, which produces an IgA (kappa) anti-phosphocholine antibody as discussed by the authors.
Abstract: We have created mouse-human antibody molecules of defined antigen-binding specificity by taking the variable region genes of a mouse antibody-producing myeloma cell line with known antigen-binding specificity and joining them to human immunoglobulin constant region genes using recombinant DNA techniques. Chimeric genes were constructed that utilized the rearranged and expressed antigen-binding variable region exons from the myeloma cell line S107, which produces an IgA (kappa) anti-phosphocholine antibody. The heavy chain variable region exon was joined to human IgG1 or IgG2 heavy chain constant region genes, and the light chain variable region exon from the same myeloma was joined to the human kappa light chain gene. These genes were transfected into mouse myeloma cell lines, generating transformed cells that produce chimeric mouse-human IgG (kappa) or IgG (kappa) anti-phosphocholine antibodies. The transformed cell lines remained tumorigenic in mice and the chimeric molecules were present in the ascitic fluids and sera of tumor-bearing mice.
2,183 citations
Journal Article•
TL;DR: It is shown that My-10 is expressed specifically on immature normal human marrow cells, including hematopoietic progenitor cells, as well as by leukemic marrow cells from a subpopulation of patients.
Abstract: The anti-My-10 mouse monoclonal antibody was raised against the immature human myeloid cell line KG-1a and was selected for nonreactivity with mature human granulocytes. Anti-My-10 immunoprecipitated a KG-1a cell surface protein with an apparent Mr of approximately 115 kD. We describe the binding of this antibody to human hematopoietic cell types and show that My-10 is expressed specifically on immature normal human marrow cells, including hematopoietic progenitor cells. My-10 is also expressed by leukemic marrow cells from a subpopulation of patients. Thus, this antibody allows the identification and purification of hematopoietic progenitor cells from normal human marrow and the subclassification of leukemia.
1,242 citations
TL;DR: A point mutation in the simian virus 40 large-T gene, which was generated by mixed oligonucleotide mutagenesis and resulted in the conversion of Lys 128 to Thr, produced a large- T antigen that was detected in the cytoplasm but not the nucleus of cells.
Abstract: A point mutation in the simian virus 40 large-T gene, which was generated by mixed oligonucleotide mutagenesis and resulted in the conversion of Lys 128 to Thr, produced a large-T antigen that was detected in the cytoplasm but not the nucleus of cells Deletions within the surrounding sequence Lys-128Lys-Lys-Arg-Lys-Val-Glu also produce cytoplasmic large-T and define a region of the protein involved in nuclear location
1,228 citations
TL;DR: Of 10 distinct cloned DNA copies of mRNAs expressed in T lymphocytes but not in B lymphocytes and associated with membrane-bound polysomes, one hybridizes to a region of the genome that has rearranged in a T- cell lymphoma and several T-cell hybridomas, suggesting that it encodes one chain of the elusive antigen receptor on the surface of T lymphocyte.
Abstract: Of 10 distinct cloned DNA copies of mRNAs expressed in T lymphocytes but not in B lymphocytes and associated with membrane-bound polysomes, one hybridizes to a region of the genome that has rearranged in a T-cell lymphoma and several T-cell hybridomas. These characteristics suggest that it encodes one chain of the elusive antigen receptor on the surface of T lymphocytes.
1,218 citations
TL;DR: A series of rat neuro/glioblastomas all contain the same transforming gene (neu) which induces synthesis of a tumour antigen of relative molecular mass (Mr) 185,000 (p185), which is serologically related to the epidermal growth factor (EGF) receptor.
Abstract: A series of rat neuro/glioblastomas all contain the same transforming gene (neu) which induces synthesis of a tumour antigen of relative molecular mass (Mr) 185,000 (p185). The neu oncogene bears homology to erb-B and the tumour antigen, p185, is serologically related to the epidermal growth factor (EGF) receptor. The two proteins, EGF receptor and p185 appear to be distinct, as they coexist in nontransformed Rat-1 cells.
1,158 citations
TL;DR: The available information leads one to conclude that APC deficient in their capacity to internalize and process proteins will not be able to present them, and the macrophage is the candidate as the major APC involved in the recruitment and enlargement of clones T cells.
Abstract: The functional significance of multiple cells--among lymphoid and nonlymphoid cells--capable of having Ia molecules on their membranes must be critically addressed. Ia is absolutely required before a cell can interact with helper T cells, but it is not clear whether the presence of this protein is all that is needed for antigen presentation. Indeed, at present, except for the macrophage, few cells have been studied for antigen presentation using a wide range of protein antigens, either soluble or particulate. On the basis of the studies discussed in the first section, it appears that the recruitment of most helper-T cell clones takes place by APC that can internalize and process the protein antigens, be they soluble or part of the structure of microorganisms. The fact that helper T cells are programmed to recognize antigen in the context of Ia, and therefore on an APC such as the macrophage, forces recognition of antigens that are altered or processed. Indeed, proteins in their native state may not remain membrane-bound for long periods; the T cells, therefore, have the opportunity to recognize the altered fragments. To this issue is added the requirement for the T-cell receptor to interact with Ia molecules. The available information, therefore, leads one to conclude that APC deficient in their capacity to internalize and process proteins will not be able to present them. The finding that small peptides from a previous catabolism of proteins can be presented without further handling implies that APC with limited processing capacity could be involved in presentation of such small peptides. The different Ia-positive APC of the lymphoid organs may interact to different extents with protein antigens and collaborate with each other to bring about an effective stimulation of the clones of helper T cells. The macrophage, being the most ubiquitous cell and the one capable of interacting with many proteins, is our candidate as the major APC involved in the recruitment and enlargement of clones T cells. The observations that macrophages can release proteins partially altered implies that there may be cooperativity among the various APC. Data for this have been obtained. Most likely B cells will be found to have a limited capacity to present all antigens because of their inherent difficulties in internalizing large particulate materials. In such instances, B cells may interact with the solubilized proteins released by the macrophages. The same may apply to the Langerhans/dendritic cells.(ABSTRACT TRUNCATED AT 400 WORDS)
1,152 citations
TL;DR: Serum samples from 88 percent of patients with AIDS and from 79 percent of homosexual men with signs and symptoms that frequently precede AIDS, but from less than 1 percent of heterosexual subjects, have antibodies reactive against antigens of HTLV-III, and the major immune reactivity appears to be directed against p41, the presumed envelope antigen of the virus.
Abstract: In cats, infection with T-lymphotropic retroviruses can cause T-cell proliferation and leukemia or T-cell depletion and immunosuppression. In humans, some highly T4 tropic retroviruses called HTLV-I can cause T-cell proliferation and leukemia. The subgroup HTLV-II also induces T-cell proliferation in vitro, but its role in disease is unclear. Viruses of a third subgroup of human T-lymphotropic retroviruses, collectively designated HTLV-III, have been isolated from cultured cells of 48 patients with acquired immunodeficiency syndrome (AIDS). The biological properties of HTLV-III and immunological analyses of its proteins show that this virus is a member of the HTLV family, and that it is more closely related to HTLV-II than to HTLV-I. Serum samples from 88 percent of patients with AIDS and from 79 percent of homosexual men with signs and symptoms that frequently precede AIDS, but from less than 1 percent of heterosexual subjects, have antibodies reactive against antigens of HTLV-III. The major immune reactivity appears to be directed against p41, the presumed envelope antigen of the virus.
1,145 citations
TL;DR: Given that T11 is the earliest T-lineage surface glycoprotein to appear in thymic ontogeny and is thus expressed before T3-Ti, the former may be involved in clonal expansion and/or differentiation during early development.
TL;DR: The expression of T and TnAntigens has pathogenic and clinical consequences, and the antigens themselves are powerful histological markers in carcinoma diagnosis and frequently in prognosis.
Abstract: Primary and metastatic carcinomas are epithelial in origin and comprise by far the largest group of malignant tumors in humans. In most of these tumors, T and Tn antigens, whose epitopes have been synthesized, are uncovered and immunoreactive. In all other tissues T and Tn antigens are masked and not accessible to the immune system; they are generally precursors in normal complex carbohydrate chains. Thus, carcinomas have antigens recognized as foreign by the patients' immune system. The expression of T and Tn antigens has pathogenic and clinical consequences, and the antigens themselves are powerful histological markers in carcinoma diagnosis and frequently in prognosis. Most patients distinguish their carcinoma from all other cells, as shown by strong autoimmune responses to T antigen. These responses are readily measured by assays, and they allow detection of carcinomas with greater sensitivity and specificity frequently earlier than previously possible. Moreover, the extent of T and Tn expression often correlates with carcinoma differentiation; on a molecular level, clustered T- and Tn-active structures on carcinoma cell surfaces may be involved in invasion.
TL;DR: A binding assay for radiolabeled monoclonal antibodies in which the fraction of immunoreactive antibody is determined by linear extrapolation to conditions representing infinite antigen excess is developed.
TL;DR: An understanding of host defense mechanisms and of the ability to distinguish self from nonself requires a knowledge of the structural basis for protein antigenicity.
Abstract: Proteins are one of the most abundant and diverse classes of antigens to which the immune system can respond. These include trarisplantation antigens, anti gens of infectious and parasitic organisms, and allergens. An understanding of host defense mechanisms and of the ability to distinguish self from nonself requires a knowledge of the structural basis for protein antigenicity. The advent of hybridoma technology ( 1 ) to produce monoclonal antibodies, each of which
TL;DR: It is shown here that unmodified monoclonal antibodies can be extremely effective at depleting cells in vivo and can be used for the selective manipulation of different aspects of the immune response.
Abstract: A major aim in immunology has been to understand how the immune system evokes characteristic responses to infection, foreign tissue grafts and tumours. The current view of immunoregulation is based mainly on studies of lymphocyte subsets, either in vitro or by adoptive transfer to irradiated recipients. Many reagents are available for defining T-cell subsets, but only recently have there been helper T-cell-specific antibodies against the mouse equivalent of the Leu3/T4 (man) and W3/25 (rat) antigens. It is clear that monoclonal antibodies will eventually replace antilymphocyte globulin for immunosuppression in organ grafting, but although there has been some clinical success, most monoclonal reagents cause only transient reductions in their target cells in vivo. This uncertainty in the potency of monoclonal antibodies has led some workers to consider them as targeting agents for such highly cytotoxic drugs as ricin A (ref. 21). We show here that unmodified monoclonal antibodies can be extremely effective at depleting cells in vivo and can be used for the selective manipulation of different aspects of the immune response.
TL;DR: Cytotoxic T cells induced by purified alloantigen are found to be as susceptible to antibody blockade as are effectors from conventional mixed lymphocyte culture, where the antibody is directed against a T-cell surface antigen reputed to strengthen target cell adhesion through an interaction independent of major histocompatibility antigens.
Abstract: Phospholipid vesicles containing the transmembrane protein H-2Kk spontaneously fuse to form planar membranes when incubated on treated glass surfaces. Pattern photobleaching of fluorescent lipid probes indicates that these planar membranes are continuous and that the lipids are as mobile as they are in conventional fluid bilayers or monolayers. H-2Kk molecules in these planar membranes are immobile. These membranes stimulate cytotoxic T lymphocytes when cultured with immune spleen cells. The response to H-2Kk in planar membranes is greatly enhanced by the addition of supernatant from concanavalin A-stimulated spleen cells, indicating that relatively little antigen processing or presentation by accessory cells occurs. Cytotoxic T cells induced by purified alloantigen are found to be as susceptible to antibody blockade as are effectors from conventional mixed lymphocyte culture, where the antibody is directed against a T-cell surface antigen reputed to strengthen target cell adhesion through an interaction independent of major histocompatibility antigens.
TL;DR: It is shown that rat astrocytes are able to present antigen to T lymphocytes in a specific manner which is restricted by the major histocompatibility complex (MHC) and that they can in particular activate myelin basic protein (BP)-specific, encephalitogenic T-cell lines.
Abstract: Astrocyte proliferation and perivascular lymphocyte infiltration are conspicuous among the cellular changes in the active brain lesions of multiple sclerosis patients1. Recent observations have indicated that most of the perivascular lymphocytes are T cells2–4 which may be actively involved in the generation of the brain lesions. Much less is known about the significance of the proliferative astrocytes, although the fact that they produce an interleukin-1 (IL-1)-like factor that enhances the release of interleukin-2 by T lymphocytes5,6, may provide a clue. We show here that rat astrocytes are able to present antigen to T lymphocytes in a specific manner which is restricted by the major histocompatibility complex (MHC) and that they can in particular activate myelin basic protein (BP)-specific, encephalitogenic T-cell lines. Only on such interaction do astrocytes express Ia antigens in easily detectable amounts. Antigen presentation by astrocytes may have a central role in the generation of immune responses in the brain.
TL;DR: During cerebellar development L1 antigen is detectable on tetanus toxin‐positive cells as early as embryonic day 13 after 3 days in culture and in the adult cerebellum, where it is predominantly localized in the molecular layer and around Purkinje cells.
Abstract: Monoclonal and polyclonal L1 antibodies react by indirect immunofluorescence with the cell surface of cultured tetanus toxin-positive neurons from post-natal cerebella of mice, but not with glial fibrillary acidic protein-positive astrocytes, O4 antigen-positive oligodendrocytes or fibronectin-positive fibroblasts or fibroblast-like cells. During cerebellar development L1 antigen is detectable on tetanus toxin-positive cells as early as embryonic day 13 after 3 days in culture. In sections of the early post-natal cerebellum, L1 antigen is found on pre-migratory neurons in the internal, but not in the external part of the external granular layer. In the adult cerebellum, L1 antigen is predominantly localized in the molecular layer and around Purkinje cells. Fibers in white matter and the granular layer are also L1 antigen-positive. Granule cell bodies and synaptic glomeruli are weakly antigen-positive. Several cell lines derived from neuroblastoma C1300 also express L1 antigen. The antigen is not detectable by enzyme-linked immunosorbent assay in tissue homogenates of liver, kidney, lung, heart, sperm or thymus. With polyclonal L1 antibodies, cross-reactive determinants are found in brains of rat, guinea pig, hamster, chicken, rabbit and man, but not in frog, while monoclonal antibody reacts detectably only with mouse brain. The molecular species recognized by both monoclonal and polyclonal antibodies display two prominent bands by SDS-PAGE under reducing and non-reducing conditions with apparent mol. wts. of 140 and 200 kd. L1 antigen isolated from cultured cerebellar cells consists mainly of a band in the 200-kd range and a faint one at 140 kd. L1 antigen from neuroblastoma N2A shows two bands with slightly higher apparent mol. wts. All molecular forms of L1 antigen can be labeled by [3H]fucose and [3H]glucosamine. Ca2+-independent re-aggregation of cerebellar cells from early post-natal C57BL/6J mice and of the continuous cell line N2A derived from the murine neuroblastoma C1300 is inhibited by Fab fragments of the polyclonal, but not of monoclonal antibody, both of which are known to react with the surface membrane of these cells.
TL;DR: It is demonstrated here that p53 can cooperate with the activated Ha-ras oncogene to transform normal embryonic cells, and the resultant foci contain cells of a markedly altered morphology which produce high levels of p53.
Abstract: The cellular tumour antigen p53 is found at elevated levels in a wide variety of transformed cells (for reviews see refs 1, 2). Very little is yet known about the precise relationship of p53 to malignant transformation. Although the increase in p53 levels could be a secondary by-product of the transformed state, it is equally possible that p53 is actively involved in altering cellular growth properties, especially as it has been implicated in the regulation of normal cell proliferation. We sought to test whether p53 could behave in a manner similar to known genes in a biological test system, and we demonstrate here that p53 can cooperate with the activated Ha-ras oncogene to transform normal embryonic cells. The resultant foci contain cells of a markedly altered morphology which produce high levels of p53. Cell lines established from such foci elicit tumours in syngeneic animals.
TL;DR: Cell lines have been established that secrete hapten-specific antibodies in which the Fc portion has been replaced either with an active enzyme moiety or with polypeptide displaying c-myc antigenic determinants.
Abstract: The introduction into lymphocytes of immunoglobulin-gene DNA that has been manipulated in vitro allows the production of novel antibodies. In this way, cell lines have been established that secrete hapten-specific antibodies in which the Fc portion has been replaced either with an active enzyme moiety or with polypeptide displaying c-myc antigenic determinants.
TL;DR: A hypothetical model is derived that relates the malignant B cell to its normal cellular counterpart on the basis of cell surface expression of this panel of B cell-restricted and B cell -associated antigens.
TL;DR: This is the first example of a vaccine produced from recombinant cells which is effective against a human viral infection, and the purified antigen in alum formulation stimulated production of antibody in mice, grivet monkeys and chimpanzees.
Abstract: The worldwide importance of human hepatitis B virus infection and the toll it takes in chronic liver disease, cirrhosis and hepatocarcinoma, make it imperative that a vaccine be developed for worldwide application. Human hepatitis B vaccines are presently prepared using hepatitis B surface antigen (HBsAg) that is purified from the plasma of human carriers of hepatitis B virus infection. The preparation of hepatitis B vaccine from a human source is restricted by the available supply of infected human plasma and by the need to apply stringent processes that purify the antigen and render it free of infectious hepatitis B virus and other possible living agents that might be present in the plasma. Joint efforts between our laboratories and those of Drs W. Rutter and B. Hall led to the preparation of vectors carrying the DNA sequence for HBsAg and antigen expression in the yeast Saccharomyces cerevisiae. Here we describe the development of hepatitis B vaccine of yeast cell origin. HBsAg of subtype adw was produced in recombinant yeast cell culture, and the purified antigen in alum formulation stimulated production of antibody in mice, grivet monkeys and chimpanzees. Vaccinated chimpanzees were totally protected when challenged intravenously with either homologous or heterologous subtype adr and ayw virus of human serum source. This is the first example of a vaccine produced from recombinant cells which is effective against a human viral infection.
TL;DR: It is established here that PCNA and cyclin are identical, and it is shown thatPCNA is an acidic nuclear protein of apparent molecular weight 35,000, which is similar to ‘cyclin’.
Abstract: Studies of growth regulation and cellular transformation will be assisted by the identification of proteins that are preferentially synthesized in dividing cells. The 'proliferating cell nuclear antigen' ( PCNA ), distinguished by its apparent association with cell division, is defined by reaction with an antibody found in the autoimmune disease systemic lupus erythematosus (SLE). This antibody reacts with proliferating cells including tumour cells but gives weak or undetectable immunofluorescence with resting cells of normal tissues. Peripheral blood lymphocytes are devoid of PCNA until activated by mitogen in vitro. In synchronized cultures its level and distribution fluctuate through the cell cycle, with a striking accumulation in the nucleolus late in the G1 phase and early in the S phase. Many of these properties are shared by ' cyclin '. This nuclear protein, identified by its position in a two-dimensional separation of cell proteins, is also transformation-sensitive and is preferentially synthesized in the S phase. We establish here that PCNA and cyclin are identical, and show that PCNA is an acidic nuclear protein of apparent molecular weight 35,000.
TL;DR: Extension of the IL-2 binding analysis to concentrations several thousand-fold higher than that necessary for the T cell proliferative response demonstrated the existence of a class (or classes) of low-affinity IL- 2 binding sites, which were found on activated T cells, several human and murine T cell lines and two examples of Tac-positive B cells.
Abstract: Interleukin 2 promotes proliferation of T cells by virtue of its interaction with a high-affinity cell surface receptor. This receptor is a 55,000 mol wt glycoprotein that is also recognized by the murine monoclonal antibody, anti-Tac. Quantitative binding studies with radiolabeled IL-2 and anti-Tac, however, initially indicated far more antibody binding sites per cell than IL-2 binding sites. Extension of the IL-2 binding analysis to concentrations several thousand-fold higher than that necessary for the T cell proliferative response demonstrated the existence of a class (or classes) of low-affinity IL-2 binding sites. Inclusion of the low-affinity IL-2 binding greatly reduced the quantitative discrepancy in the ligand binding assays. That the low-affinity binding, as well as the high-affinity interaction, was associated with the Tac molecule was indicated by the finding that the antibody could substantially or totally block the entire spectrum of IL-2 binding and by the finding that IL-2 could in turn block all radiolabeled anti-Tac binding. The low-affinity sites were found on activated T cells, several human and murine T cell lines and two examples of Tac-positive B cells. The physiological role of the low-affinity IL-2 binding sites and the molecular changes in the Tac protein that give rise to the affinity differences remain open to investigation.
TL;DR: Another subgroup of HTLV, designated HTLV-III, has now been isolated from many patients with AIDS and pre-AIDS and is shown to be a true member of the HTLV family.
Abstract: The two main subgroups of the family of human T-lymphotropic retroviruses (HTLV) that have previously been characterized are known as HTLV-I and HTLV-II Both are associated with certain human leukemias and lymphomas Cell surface antigens (p61 and p65) encoded by HTLV-I are frequently recognized, at low titers, by antibodies in the serum of patients with acquired immunodeficiency syndrome (AIDS) or with signs or symptoms that precede AIDS (pre-AIDS) This suggests an involvement of HTLV in these disorders Another subgroup of HTLV, designated HTLV-III, has now been isolated from many patients with AIDS and pre-AIDS In the studies described in this report, virus-associated antigens in T-cell clones permanently producing HTLV-III were subjected to biochemical and immunological analyses Antigens of HTLV-III, specifically detected by antibodies in serum from AIDS or pre-AIDS patients and revealed by the Western blot technique, are similar in size to those found in other subgroups of HTLV They include at least three serologically unrelated antigenic groups, one of which is associated with group-specific antigens (p55 and P24) and another with envelope-related (p65) proteins, while the antigens in the third group are of unknown affiliation The data show that HTLV-III is clearly distinguishable from HTLV-I and HTLV-II but is also significantly related to both viruses HTLV-III is thus a true member of the HTLV family
TL;DR: The development of anti-ATLA in the recipients may correspond to antibody production after establishment of primary infection with ATLV that is associated with cells in blood from anti‐ATLA‐positive donors who are ATLV carriers.
Abstract: Possible transmission of adult T cell leukemia virus (ATLV) by blood transfusion was studied retrospectively. Of 41 recipients of whole blood or blood components containing cells from donors having antibodies to antigen that is associated with ATLV (anti-ATLA), 26 (63.4%) produced anti-ATLA. However, no anti-ATLA was detected in all 14 recipients of fresh-frozen plasma prepared from anti-ATLA-positive donors. None of 252 recipients of blood with cell components from anti-ATLA-negative donors produced anti-ATLA. The development of anti-ATLA in the recipients may correspond to antibody production after establishment of primary infection with ATLV that is associated with cells in blood from anti-ATLA-positive donors who are ATLV carriers.
TL;DR: It is concluded that Ly-1 B cells constitute a functionally distinct B-cell population important in certain kinds of autoimmunity.
Abstract: Studies presented here introduce another perspective on the mechanisms responsible for IgM autoantibody production. A unique subpopulation of B lymphocytes (Ly-1 B) that concomitantly expresses IgM, IgD, Ia, and Ly-1 membrane glycoproteins is present at higher frequencies in NZB and NZB-related mice. The Ly-1 B subpopulation in these autoimmune animals is responsible for the "spontaneous" IgM secretion demonstrated with cultured NZB spleen cells and contains the cells that secrete typical NZB IgM autoantibodies to single-stranded DNA and to thymocytes. In addition, the Ly-1 B population in normal mouse strains (and in NZB) contains virtually all of the spleen cells that secrete IgM autoantibodies reactive with bromelain-treated mouse erythrocytes. Since a different B-cell subpopulation (IgM+, IgD-, Ly-1) secretes most of the IgM antibodies produced in responses to exogenous antigens, we conclude that Ly-1 B cells constitute a functionally distinct B-cell population important in certain kinds of autoimmunity.
TL;DR: Results demonstrate that the DF3 antigen is present on apical borders of more differentiated secretory mammary epithelial cells and in the cytosol of less differentiated cells.
Abstract: We have defined a human breast tumor associated antigen using a murine monoclonal antibody (MAb DF3) prepared against a membrane-enriched fraction of a human breast carcinoma. This antigen has a MW of 290 kD and is detectable on the cell surface of human breast carcinoma cells using a live cell radioimmunoassay and fluorescence flow cytometry. More important, immunoperoxidase staining with MAb DF3 clearly distinguishes malignant and benign breast lesions. A cytoplasmic staining pattern has been observed with 40 of 51 (78%) breast carcinomas, but only one of 13 fibroadenoma or fibrocystic disease specimens. In contrast, reactivity of benign breast lesions with MAb DF3 primarily occurs along apical borders on ductules. These results demonstrate that the DF3 antigen is present on apical borders of more differentiated secretory mammary epithelial cells and in the cytosol of less differentiated cells.
TL;DR: This article showed that IFN-γ induces a dramatic increase in the expression of H−2 antigens on the cells of the brain, including most surviving cells including most astrocytes, oligodendrocyte, microglia and at least some neurones.
Abstract: Cells in the brain express unusually low levels of antigens encoded by the major histocompatibility complex (MHC)1,2. This is somewhat surprising as class I (H−2) and class II (Ia) MHC antigens have critical roles in immune responses3. The activation of T lymphocytes is associated with the enhanced expression of these antigens and this effect is mediated by a specific T-cell lymphokine, γ-interferon (IFN-γ)4–17. Here we show that IFN-γ induces a dramatic increase in the expression of H–2 antigens on the cells of the brain. After exposure to IFN-γ in vitro, all surviving cells, including most astrocytes, oligodendrocytes, microglia and at least some neurones, express H–2 antigens. Direct injection of IFN-γ into the brains of mice indicated that H–2 antigens were also induced in vivo. Furthermore, IFN-γ induced Ia antigens on a subpopulation of astrocytes. The induction of H–2 antigens by IFN-γ may render brain cells competent to initiate and participate in immune reactions and may therefore contribute to both immunoprotective and immunopathological responses in the brain.