The Immunosuppressive Peptide of HIV-1 Inhibits T and B Lymphocyte Stimulation

Abstract

Summary: The transmembrane glycoproteins of all retroviruses contain a conserved region composed of a leucine zipper, an immunosuppressive domain, and an immunodominant Cys-Cys loop. The amino acid sequence of the immunosuppressive domain of gp41 of human immunodeficiency virus type 1 (HIV-1; amino acids 583-599) is closely related, but not identical, to the immunosuppressive domains of type C and D retroviruses. A synthetic peptide corresponding to the immunosuppressive domain of HIV-1 (immunosuppressive peptide, ISU-peptide) inhibits mitogen and lymphokine stimulation of T lymphocytes. It is interspecies reactive and inhibits both human and mouse lymphocytes. The inhibitory effect is not based on direct cytotoxicity and the peptide is immunosuppressive only when conjugated to a carrier protein. The ISU-peptide of HIV-1 also inhibits B lymphocyte stimulation by the B cell mitogen lipopolysaccharide and by specific antibodies against δ and μ chains of cell surface immunoglobulins. These data suggest that the immunosuppressive domain of gp41 may play an important role in the immunopathogenesis of AIDS.