Respiratory syncytial virus (RSV) is the most important cause of viral lower respiratory tract illness in infants and children throughout the world. The immune correlates of protection and resolution of infection are not well defined. Experiments in animal models suggest that RSV induces cytolytic T cells (CTL) that are important to clearance of virus infection. The importance of RSV-specific T cells in the human response to infection is unknown. Currently, reagents and techniques do not exist for the study of RSV-specific T cells in humans. The specific aim of this proposal is to identify the epitope specificity and MHC restriction of RSV nucleoprotein-specific CD8+ CTL in adults. Human peripheral blood mononuclear cells will be used as a source of CD8+ lymphocytes to map the epitope specificity and define the MHC class I allelic restriction of RSV-specific CTL. Defining CTL epitopes will allow improvements in the sensitivity of CTL detection, and provide an opportunity to perform precursor frequency analysis. This project enhances the U.S. Investigator's NIH-supported research by studying the molecular basis for RSV-specific T-cell reactivity, thereby complementing work on RSV-specific B cell responses. The two projects fall within the same area of investigation, namely molecular definition of determinants of human immune responses to RSV, but do not overlap because one studies humoral and the other cellular immunity. Together the grants will allow a coordinated investigation of the major mediators of resistance to infection with RSV.