Handling of retroviral antigens by human antigen-presenting cells.
Antigen-specific T helper cells play an important role in retroviral infections. Indeed, they provide help for B-cell activation and antibody production and for clonal expansion of cytolytic lymphocytes. Therefore, we used retrovirus-specific human T helper clones in order to define modes of antigen presentation, antigen-presenting cells and the molecular context of Th epitopes that could be exploited in the design of immunogens aimed at optimizing the Th cell response. In particular, we describe several mechanisms of receptor-mediated antigen uptake that enhance the stimulation of human T-cell clones specific for HIV and HTLV-1 antigens; we report on the differential recognition of Th epitopes depending on the molecular-viral context; we show that dendritic cells are the most efficient presenting cells and are essential for the induction of in vitro primary Th cell responses; and finally, we propose that Th cells specific for internal, conserved antigens of HIV such as reverse transcriptase, may be candidates for intrastructural help resulting in induction of envelope specific antibodies.
Department of Immunology, University of Genoa, Italy.
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Fenoglio
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Li Pira
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Oppezzi
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Piatti
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Buffa
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Kunkl
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D017951:Antigen Presentation; D000938:Antigen-Presenting Cells / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000737:chemistry / Q000276:immunology / Q000473:pathology; D000939:Epitopes / Q000276:immunology; D015686:Gene Products, env / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D016655:HIV Core Protein p24 / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D019302:HIV Envelope Protein gp160 / Q000276:immunology; D054303:HIV Reverse Transcriptase / Q000276:immunology*; D015486:HTLV-I Antigens / Q000276:immunology*; D006801:Humans; D009000:Monocytes / Q000737:chemistry / Q000276:immunology / Q000502:physiology; D011961:Receptors, Fc / Q000276:immunology; D011994:Recombinant Proteins / Q000276:immunology; D015682:Retroviridae Proteins, Oncogenic / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D000939:Epitopes; D015686:Gene Products, env; D015488:HIV Antigens; D016655:HIV Core Protein p24; D015699:HIV Envelope Protein gp120; D019302:HIV Envelope Protein gp160; D015486:HTLV-I Antigens; D011961:Receptors, Fc; D011994:Recombinant Proteins; D015682:Retroviridae Proteins, Oncogenic; C055266:gp46 protein, Human T-cell leukemia virus type I; D054303:HIV Reverse Transcriptase