V3 loop of human immunodeficiency virus type 1 suppresses interleukin 2-induced T cell growth.
We tested the effect of three linear or two loop peptides derived from the V3 region of the HTLV-III BH10 clone or the SF2 strain of human immunodeficiency virus type 1 on IL-2-driven T cell proliferation. V3-BH10, which consists of 42 amino acids and has a loop structure, suppressed IL-2-driven proliferation of all IL-2-dependent cells [Kit225, ED-40515(+), KT-3, 7-day PHA-blasts, and fresh peripheral blood mononuclear cells] tested, whereas it did not suppress the cell growth of IL-2-independent cell lines (Hut102, Molt-4, and Jurkat). This suppressive effect was also seen in IL-2-driven cell growth of CD8-positive lymphocytes purified from 7-day PHA-blasts, indicating that CD4 molecules were not required for the suppression. The treatment with anti-V3 loop monoclonal antibody (902 antibody) completely abolished the suppressive effect of V3-BH10. In addition, V3-BH10 generated the arrest of Kit225 cells and also purified CD8-positive lymphocytes in G1 phase in the presence of IL-2. Neither chromatin condensation nor DNA fragmentation was detected in Kit225 cells cultured with V3-BH10 and IL-2. V3-BH10 neither blocked radiolabeled IL-2 binding to IL-2 receptors nor affected tyrosyl phosphorylation of several cellular proteins (p120, p98, p96, p54, and p38), which is immediately induced by IL-2 stimulation. However, V3-BH10 enhanced IL-2-induced mRNA expression of c-fos but not c-myc or junB. Thus, the binding of V3 loop of gp120 to the cell surface molecule(s) appears to affect intracellular IL-2 signaling, which leads to the suppression of IL-2-induced T cell growth.
Sakaida
H
H
Laboratory of AIDS Immunology, Research Center for Immunodeficiency Virus, Institute for Virus Research, Kyoto University, Japan.
Murakami
T
T
Kawamata
S
S
Hattori
T
T
Uchiyama
T
T
D000595:Amino Acid Sequence; D001562:Benzimidazoles; D002453:Cell Cycle; D002455:Cell Division; D002843:Chromatin; D005456:Fluorescent Dyes; D015870:Gene Expression / Q000187:drug effects; D006131:Growth Inhibitors / Q000502:physiology*; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D007376:Interleukin-2 / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000502:physiology*; D010766:Phosphorylation; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000821:virology; D014407:Tumor Cells, Cultured; D014443:Tyrosine
D001562:Benzimidazoles; D002843:Chromatin; D005456:Fluorescent Dyes; D006131:Growth Inhibitors; D015699:HIV Envelope Protein gp120; C059762:HIV envelope protein gp120 (305-321); D007376:Interleukin-2; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D014443:Tyrosine; C017807:bisbenzimide ethoxide trihydrochloride