Characterization of Nef-induced CD4 T cell proliferation.
Studies on Nef, a regulatory protein encoded by human immunodeficiency virus (HIV), suggest it plays an important role in HIV pathogenesis. Previously, we reported that Nef binds to class II MHC antigens and induces proliferation of human peripheral blood mononuclear cells (PBMC). Herein, we further characterize PBMC responses to Nef. Polyclonal antisera generated against Nef synthetic peptides blocked proliferation. Responses were T cell-specific and required antigen-presenting cells (APC). T cells responded in the presence of paraformaldehyde-inactivated APC, suggesting that Nef is presented in an unprocessed form. Nef-stimulated cells produced IL 2 and IFN gamma, products of T helper-1 cells. Thus, Nef has superantigen properties in that it binds to MHC class II antigens, does not need processing to be presented by APC, and activates T cells, causing proliferation and production of the T helper 1 cytokines, IL 2 and IFN gamma. The identification of an HIV protein that activates T cells is of considerable interest, given that HIV replicates in T cell blasts but not in quiescent cells.
Torres
B A
BA
Department of Microbiology and Cell Science, University of Florida, Gainesville 32611, USA.
Tanabe
T
T
Johnson
H M
HM
D000328:Adult; D000906:Antibodies / Q000494:pharmacology; D000938:Antigen-Presenting Cells / Q000276:immunology; D001483:Base Sequence; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D002478:Cells, Cultured; D003208:Concanavalin A; D017931:DNA Primers; D004768:Enterotoxins / Q000494:pharmacology; D015693:Gene Products, nef / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology*; D018023:HIV Seronegativity / Q000276:immunology; D015497:HIV-1 / Q000378:metabolism; D006801:Humans; D007135:Immunoglobulin Variable Region; D007371:Interferon-gamma / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000302:isolation & purification; D013211:Staphylococcus aureus; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D054311:nef Gene Products, Human Immunodeficiency Virus
D000906:Antibodies; D017931:DNA Primers; D004768:Enterotoxins; D015693:Gene Products, nef; D007135:Immunoglobulin Variable Region; D007376:Interleukin-2; D010446:Peptide Fragments; D011993:Recombinant Fusion Proteins; D054311:nef Gene Products, Human Immunodeficiency Virus; D003208:Concanavalin A; C026066:enterotoxin A, Staphylococcal; D007371:Interferon-gamma