Methods for stimulating immune responses in a host through the administration of superantigen peptides derived from human immunodeficiency virus type 1 Nef

摘要

The human immunodeficiency virus (HIV) contains, in addition to the canonical genes gag, pol, and env, an open reading frame in the 3' region of the genome that overlaps with the 3' long terminal repeat (LTR). Initial studies on the protein encoded by this ORF revealed a negative effect on HIV replication in vitro and this gene product was subsequently designated the negative factor, or Nef. The nef gene product is 25-29 kDa protein that localizes primarily to the cytoplasm of HIV-infected cells. The subject of this invention pertains to the discovery of a superantigen activity associated with this peptide and peptidic fragments derived therefrom. Superantigens are powerful T-cell mitogens that bind directly to major histocompatibility complex (MHC) class II molecules and form a binary complex with the variable (V. sub.) region of the T- cell antigen receptor (TCR). It was demonstrated that Nef induces the rapid proliferation of human peripheral mononuclear cells and T- lymphocyte cytokine production. Nef peptidic fragments were also identified that display major histocompatibility complex (MHC) class II binding activity. These peptides can be utilized to generate suitable immune responses in the desired host.