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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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Journal ArticleDOI
06 Apr 2006-Nature
TL;DR: It is shown that the efficiency of presenting antigens from phagocytosed cargo is dependent on the presence of TLR ligands within the cargo and the generation of peptide–MHC class II complexes is controlled by TLRs in a strictly phagosome-autonomous manner.
Abstract: Dendritic cells constitutively sample the tissue microenvironment and phagocytose both microbial and host apoptotic cells. This leads to the induction of immunity against invading pathogens or tolerance to peripheral self antigens, respectively. The outcome of antigen presentation by dendritic cells depends on their activation status, such that Toll-like receptor (TLR)-induced dendritic cell activation makes them immunogenic, whereas steady-state presentation of self antigens leads to tolerance. TLR-inducible expression of co-stimulatory signals is one of the mechanisms of self/non-self discrimination. However, it is unclear whether or how the inducible expression of co-stimulatory signals would distinguish between self antigens and microbial antigens when both are encountered by dendritic cells during infection. Here we describe a new mechanism of antigen selection in dendritic cells for presentation by major histocompatibility complex class II molecules (MHC II) that is based on the origin of the antigen. We show that the efficiency of presenting antigens from phagocytosed cargo is dependent on the presence of TLR ligands within the cargo. Furthermore, we show that the generation of peptide-MHC class II complexes is controlled by TLRs in a strictly phagosome-autonomous manner.

815 citations

Journal Article
TL;DR: Data implicate IFN-gamma as a suppressive factor for the proliferation of the subset of HTL designated Th2, and suggest that the relative amounts of the various lymphokines present during an immune response may direct which T cell types increase in number.
Abstract: A biphasic dose-response curve was observed when the IL-1-dependent HTL clone D10 was exposed to IL-1 plus supernatants from some activated T cell clones but not others. The active component that inhibited proliferation at high concentrations of these supernatants appeared to be IFN-gamma based on the following findings: 1) the biphasic pattern of responsiveness correlated with the presence of IFN-gamma in the supernatants; 2) an anti-IFN-gamma mAb augmented the proliferation of D10 cells to these supernatants; 3) rIFN-gamma inhibited profoundly the response of D10 cells stimulated with rIL-1 plus supernatant from activated D10 cells or with rIL-1 plus rIL-4; 4) the response of D10 cells to rIL-1 plus rIL-2 also was inhibited by rIFN-gamma, although to a lesser extent. The proliferation of an additional Th2 clone stimulated with rIL-1 plus rIL-4 or rIL-2 also was inhibited by rIFN-gamma, implicating IFN-gamma as an inhibitory lymphokine for Th2 cells in general. rIFN-gamma did not affect the proliferation of two Th1 clones, nor did it affect the proliferation of an unconventional HTL clone which produces both IL-4 and IFN-gamma and proliferates in response to IL-2 or IL-4 in an IL-1-independent fashion. The proliferation of D10 cells stimulated by Ag or by immobilized anti-CD3 antibody also was blocked by rIFN-gamma, whereas IL-4 production in response to these stimuli was unaffected, indicating that proliferation and not general cell function was specifically inhibited. Collectively, these data implicate IFN-gamma as a suppressive factor for the proliferation of the subset of HTL designated Th2, and suggest that the relative amounts of the various lymphokines present during an immune response may direct which T cell types increase in number.

812 citations

Journal ArticleDOI
TL;DR: Triggering of BDCA-2 should be evaluated as therapeutic strategy for blocking production of interferon alpha/beta in systemic lupus erythematosus patients.
Abstract: Plasmacytoid dendritic cells are present in lymphoid and nonlymphoid tissue and contribute substantially to both innate and adaptive immunity. Recently, we have described several monoclonal antibodies that recognize a plasmacytoid dendritic cell-specific antigen, which we have termed BDCA-2. Molecular cloning of BDCA-2 revealed that BDCA-2 is a novel type II C-type lectin, which shows 50.7% sequence identity at the amino acid level to its putative murine ortholog, the murine dendritic cell–associated C-type lectin 2. Anti–BDCA-2 monoclonal antibodies are rapidly internalized and efficiently presented to T cells, indicating that BDCA-2 could play a role in ligand internalization and presentation. Furthermore, ligation of BDCA-2 potently suppresses induction of interferon α/β production in plasmacytoid dendritic cells, presumably by a mechanism dependent on calcium mobilization and protein-tyrosine phosphorylation by src-family protein-tyrosine kinases. Inasmuch as production of interferon α/β by plasmacytoid dendritic cells is considered to be a major pathophysiological factor in systemic lupus erythematosus, triggering of BDCA-2 should be evaluated as therapeutic strategy for blocking production of interferon α/β in systemic lupus erythematosus patients.

811 citations

Journal ArticleDOI
14 Jul 2006-Cell
TL;DR: A specialization of the phagocytic pathway of DCs is described that allows a fine control of antigen processing and plays a critical role in conferring DCs the ability to function as specialized phagocytes adapted to process antigens rather than kill pathogens.

811 citations

Journal Article
TL;DR: The immunosuppressive effect of the presence of thymocytes during the antigen Pretreatment was studied by adoptively transferring the spleen cells of the antigen pretreated mice to thymus-deprived chimeras.
Abstract: Previous studies have shown that thymectomized lethally irradiated bone marrow grafted mice, reconstituted with thymocytes and pretreated with a large dose of sheep red blood cells (SRBC), are unable to respond to a subsequent immunizing injection of SRBC even after an inoculation of normal thymocytes. If, however, the mice are not thymocyte reconstituted prior to the pretreatment with SRBC, they can respond almost normally to an immunizing injection of SRBC if inoculated with normal thymocytes after the termination of antigen pretreatment.In the present study the immunosuppressive effect of the presence of thymocytes during the antigen pretreatment was studied by adoptively transferring the spleen cells of the antigen pretreated mice to thymus-deprived chimeras. These spleen cells not only did not co-operate with normal thymocytes in the secondary hosts, but they also prevented the co-operation of normal thymocytes with normal bone marrow derived cells. Untreated spleen cells or treated spleen cells from mice not reconstituted with thymocytes did not affect cell co-operation in the secondary hosts. The abrogation of the co-operation in the secondary host was specific in that the addition of spleen cells did not affect the anti-horse red blood cell response. If the primary host made antibody as a result of the pretreatment, the transfer of their spleen cells did not prevent antibody production in the secondary host.

811 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
20244
20233,983
20225,279
20213,228
20203,444
20193,267