Multiple cis-acting elements in the human immunodeficiency virus type 2 enhancer mediate the response to T-cell receptor stimulation by antigen in a T-cell hybridoma line.
Transcription directed by the human immunodeficiency virus type 2 long terminal repeat (HIV-2 LTR) responds to T-cell antigen receptor signaling. Agents that stimulate T-cell signaling pathways activated by the antigen receptor, such as phorbol ester, plant lectin, or anti-CD3 antibody treatment, have been shown to increase transcription directed by the HIV-2 LTR. In this study, we examine the activation of the HIV-2 LTR in T cells stimulated with the physiologic ligand of the T-cell receptor, antigenic peptide presented by a major histocompatibility molecule. HIV-2 reporter plasmids were transfected into the antigen-specific T-cell hybridoma, 2B4.11, where they responded to antigen-dependent activation. This antigen-mediated transcriptional activation of the HIV-2 enhancer required the presence of at least four regulatory elements in the HIV-2 enhancer, including two purine boxes, PuB1 and PuB2, an AP-1/CREB-like element (pets), and kappa B. This finding suggests that signals emanating from the antigen receptor act coordinately on a set of transcription factors that bind to conserved HIV-2 regulatory elements. Despite differences in the organization of potentially related enhancer elements in HIV-2 and IL-2, these enhancers exploit a similar signal transduction pathway to induce gene expression in antigen-activated T cells.
Hannibal
M C
MC
Howard Hughes Medical Institute, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0650.
Markovitz
D M
DM
Nabel
G J
GJ
D000818:Animals; D000938:Antigen-Presenting Cells / Q000502:physiology; D000941:Antigens / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D004742:Enhancer Elements, Genetic; D005809:Genes, Regulator; D016325:HIV Long Terminal Repeat; D015498:HIV-2 / Q000235:genetics*; D006801:Humans; D006825:Hybridomas; D051379:Mice; D008969:Molecular Sequence Data; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology*; D014158:Transcription, Genetic
D000941:Antigens; D011948:Receptors, Antigen, T-Cell