Vaccine research demands highly accurate and sensitive testing methods. My lab pioneered the development of tetramer reagents, which can be customized for individual studies to provide extremely precise measures of immune response. Our current research programs center around our breakthrough tetramer technology that we use to directly identify antigen-specific T cells by staining with tetrameric forms of soluble MHC/peptide complexes that have enhanced avidity for cells bearing specific T cell antigen receptors (TCR). Using a mouse model of the CD8+ T cell response to infection with LCMV (a collaborative project with Dr. Rafi Ahmed) we are investigating factors that control the development of the antigen-specific T cell repertoire. Outstanding questions that we seek to answer include: 1) does antigen density affect the repertoire of T cells recruited during an immune response, as predicted by avidity models?; and 2) are antigen-specific memory T cells selected from among the larger primary responding population based on additional interactions mediated by the T cell antigen receptor? We also are applying tetramer technology to clinically relevant studies assessing immune function in HIV-infected individuals on potent anti-retroviral therapy, and applied studies to assess AIDS vaccine efficacy in a rhesus macaque model. We plan to follow up these studies to examine the effects of highly active antiretroviral therapy (HAART) on the frequency and function of HIV-specific CD8+ T cells. Finally, we plan to use the MHC tetramers to assess vaccine development studies in the rhesus macaque model.