APOPTOSIS INDUCTION BY HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 (HIV-1) GP120 PEPTIDES

We investigated the role of some gp120 peptides on the apoptosis induc tion in malignant T cell lines. We took advantage of recent findings r eporting that three major regions of gp120 are important for CD4 bindi ng. They consist of residues 256-262 in the C2 domain, residues 368-38 9 in the C3 domain, and residues 421-457 in C4 domain. We used a pepti de from C2 domain (aa 250-263) the homologous major histocompatibility complex (MHC) class II peptide (aa 135-155) and three peptides from d omain C4 (aa 464-434; 419-430; 428-445), We selected for this study th e following human cell lines: CEM and Jurkat, two lymphoblastoid CD4-p ositive T cell line and U937, a myelomonocytic CD4 positive cell line. We demonstrated that the CD4-positive T cell lines, in the presence o f gp120 250-263 peptide and DR 135-155 peptide, can be induced to acce lerate apoptosis, while no effect in apoptosis induction was observed in the presence of 414-424 gp120 peptide, Interestingly, we have shown by fluorescence study, that the small sequence 414-419 must be respon sible for the inhibition of binding of gp120 to the CD4 molecule, Inde ed while 414-424 gp120 peptide is very efficient in CD4-gp120 binding inhibition, no effect is observed in the presence of either 419-430 or 428-445 peptide.