Topic
Antigen
About: Antigen is a research topic. Over the lifetime, 170233 publications have been published within this topic receiving 6982342 citations. The topic is also known as: antibody generator & Antigen.
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TL;DR: It is demonstrated that modifications that reroute a cytosolic tumor antigen to the endosomal/lysosomal compartment can profoundly improve the in vivo therapeutic potency of recombinant vaccines.
Abstract: Presentation of antigenic peptides by MHC class II molecules to CD4+ T cells is critical to the generation of antitumor immunity. In an attempt to enhance MHC class II antigen processing, we linked the sorting signals of the lysosome-associated membrane protein (LAMP-1) to the cytoplasmic/nuclear human papilloma virus (HPV-16) E7 antigen, creating a chimera (Sig/E7/LAMP-1). Previously, we found that expression of this chimera in vitro and in vivo with a recombinant vaccinia vector targeted E7 to endosomal and lysosomal compartments and enhanced MHC class II presentation to CD4+ T cells compared to vaccinia expressing wild-type E7. In the current study, we tested these recombinant vaccinia for in vivo protection against an E7+ tumor, TC-1, which was derived from primary epithelial cells of C57BL/6 mice cotransformed with HPV-16 E6 and E7 and c-Ha-ras oncogenes. All mice vaccinated with 1 x 10(7) plaque-forming units of wild-type E7-vaccinia showed progressive tumor growth when challenged with a tumorigenic dose of TC-1 tumor cells; in contrast, 80% of mice vaccinated with the chimeric Sig/E7/LAMP1 vaccinia remained tumor free 3 months after tumor injection. Furthermore, treatment with the Sig/E7/LAMP-1 vaccinia vaccine cured mice with small established TC-1 tumors, whereas the wild-type E7-vaccinia showed no effect on this established tumor burden. These findings point out the therapeutic limitations of recombinant vaccinia expressing unmodified tumor antigens. Further, they demonstrate that modifications that reroute a cytosolic tumor antigen to the endosomal/lysosomal compartment can profoundly improve the in vivo therapeutic potency of recombinant vaccines.
1,015 citations
TL;DR: These experiments imply that commitment of T cells to participate exclusively in either helper or cytotoxic function is a differentiative process that takes place before they encounter antigen, and is accompanied by exclusion of different Ly groups, Lu-23 or Ly-1 respectively, from TL+Ly-123+ T-cell precursors.
Abstract: Ly alloantigens coded by two unlinked genetic loci (Ly-1 and Ly-2/Ly-3) are expressed on lymphoid cells undergoing thymus-dependent differentiation. Peripheral Thy-1+ cells from C57BL/6 mice can be divided into three subclasses on the basis of differential expression of Ly-1, Ly-2, and Ly-3; about 50% express all three Ly antigens (Ly -123+), about 33% only Ly-1 (Ly-1+), and about 6-8% Ly-2 and Ly-3 (Ly-23+). Cells of the Ly-123+ subclasses are the first peripheral Thy-1+ cells to appear in ontogeny, and are reduced in the periphery shortly after adult thymectomy. In contrast, Ly-1+ and Ly-23+ subclasses appear later in the peripheral tissues than do Ly-123+ cells, and are resistant to the early effects of adult thymectomymperiheral lymphoid populations depleted of Ly-1+ cells and Ly-123+ cells (and thereby enriched for Ly-23+ cells) were incapable of developing significant helper activity to SRBC but generated substantial levels of cytotoxic activity to allogeneic target cells. The same lymphoid populations, depleted of Ly-23+ cells and Ly-123+ cells (and thereby enriched for Ly-1+ cells), produced substantial helper responses but were unable to generate appreciable levels of killer activity. These experiments imply that commitment of T cells to participate exclusively in either helper or cytotoxic function is a differentiative process that takes place before they encounter antigen, and is accompanied by exclusion of different Ly groups, Lu-23 or Ly-1 respectively, from TL+Ly-123+ T-cell precursors. It is yet to be decided whether the TL-phase by Ly-123+ subclass is a transitional form or a separately differentiated subclass with a discrete immunologic function.
1,015 citations
TL;DR: The activation of NKT cells paradoxically can lead either to suppression or stimulation of immune responses, and one cannot predict which will occur, and many investigators are hopeful that immune therapies can be developed based on NKT cell stimulation.
Abstract: Natural killer T (NKT) cells constitute a conserved T cell sublineage with unique properties, including reactivity for a synthetic glycolipid presented by CD1d, expression of an invariant T cell antigen receptor (TCR) alpha chain, and unusual requirements for thymic selection. They rapidly produce many cytokines after stimulation and thus influence diverse immune responses and pathogenic processes. Because of intensive research effort, we have learned much about factors promoting the development and survival of NKT cells, regulation of their cytokine production, and the means by which they influence dendritic cells and other cell types. Despite this progress, knowledge of the natural antigen(s) they recognize and their physiologic role remain incomplete. The activation of NKT cells paradoxically can lead either to suppression or stimulation of immune responses, and we cannot predict which will occur. Despite this uncertainty, many investigators are hopeful that immune therapies can be developed based on NKT cell stimulation.
1,014 citations
TL;DR: This chapter summarizes the known information on the expression of natural cytotoxicity in rodents and in man, its specificity, the nature of the effector cells and their relationship to other immune mechanisms, and the possible in vivo relevance ofnatural cytotoxic relevance, particularly in regard to resistance against tumor growth.
Abstract: Publisher Summary The recognition of the existence of natural cell-mediated immunity, particularly natural cell-mediated cytotoxicity, has significantly altered the concepts concerning the potential mechanisms for in vivo resistance against tumor growth and for in vitro cell-mediated immune reactions. When cytotoxic reactions are measured, the evaluation of the role of natural killer (NK) cells and other more well-known mechanisms of cytotoxicity must be done carefully. This chapter focuses on natural cell-mediated cytotoxicity. It summarizes the known information on the expression of natural cytotoxicity in rodents and in man, its specificity, the nature of the effector cells and their relationship to other immune mechanisms, and the possible in vivo relevance of natural cytotoxicity, particularly in regard to resistance against tumor growth. The basic observation that initiated the studies of natural cell mediated cytotoxicity includes that lymphoid cells from some normal mice, rats, and human donors, which are not inoculated with tumor cells or other sources of antigen, exhibit significant levels of cytotoxic reactivity against certain syngeneic or allogeneic tumor cells.
1,013 citations
TL;DR: A potential approach to therapy in which autologous CD8 lymphocytes could be administered to individuals to inhibit HIV replication and perhaps progression of disease is suggested.
Abstract: Lymphocytes bearing the CD8 marker were shown to suppress replication of human immunodeficiency virus (HIV) in peripheral blood mononuclear cells. The effect was dose-dependent and most apparent with autologous lymphocytes; it did not appear to be mediated by a cytotoxic response. This suppression of HIV replication could be demonstrated by the addition of CD8+ cells at the initiation of virus production as well as after several weeks of virus replication by cultured cells. The observations suggest a potential approach to therapy in which autologous CD8 lymphocytes could be administered to individuals to inhibit HIV replication and perhaps progression of disease.
1,012 citations