Human immunodeficiency virus type 1 envelope epitope-specific CD4(+) T lymphocytes in simian/human immunodeficiency virus-infected and vaccinated rhesus monkeys detected using a peptide-major histocompatibility complex classII tetramer

A tetrameric recombinant major histocompatibility complex (MHC) class II-pe ptide complex was used to quantitate human immunodeficiency virus type 1 (H IV-1) envelope (Env)-specific CD4(+) T cells in vaccinated and in simian/hu man immunodeficiency virus (SHIV)-infected rhesus monkeys. A rhesus monkey MHC class II DR molecule, Mamu-DR*W201, and an HIV-1 Env peptide (p46) were employed to construct this tetrameric complex. A p46 specific proliferativ e response was seen in sorted, tetramer-binding, but not nonbinding, CD4(+) T cells, directly demonstrating that this response was mediated by the epi tope-specific lymphocytes. Although staining of whole blood from 10 SHIV-in fected Mamu-DR*W201(+) rhesus monkeys failed to demonstrate tetramer-bindin g CD4(+) T cells (<0.02%), p46-stimulated peripheral blood mononuclear cell s (PBMCs) from 9 of these 10 monkeys had detectable p46 tetramer-binding ce lls, comprising 0.5 to 15.2% of the CD4(+) T cells. p46-stimulated PBMCs fr om 7 of 10 Mamu-DR*W201(+) monkeys vaccinated with a recombinant canarypox virus-HIV-1 env construct also demonstrated p46 tetramer-binding cells, com prising 0.9 to 7.2% of the CD4(+) T cells. Thus, Env p46-specific CD4(+) T cells can be detected by tetrameric Mamu-DR*W201-p46 complex staining of PB MCs in both SHIV-infected and vaccinated rhesus monkeys. These epitope-spec ific cell populations appear to be present in peripheral blood at a very lo w frequency.