This project will investigate the cellular and molecular mechanisms that operate to produce the cytotoxic CD8+ T lymphocyte (CTL) response to Equine Herpesvirus type 1 (EHV-1) that is considered to be a critical component of immunity to this virus. Current vaccines against EHV-1 provide partial clinical and virological protection in horses, particularly against abortion and neurological disease, but CTL responses to the modified live virus (MLV) vaccine have not been studied in detail. In this revised application we propose to test the overall hypothesis that equine CTL that are associated with protection against EHV-1 recognize a limited number of viral target proteins. This hypothesis is based on several lines of evidence, including studies of horses naturally infected with EHV-1. On a very practical level, this research will determine if horses vaccinated with the commercial MLV vaccine make the same type of T-cell responses observed in horses that have recovered from active infection. On a more theoretical level we will study the phenomenon of immunodominance to viral infections as it applies to EHV-1 in horses. Immunodominance limits the number of viral proteins that are recognized by the host immune system through several known cellular and molecular mechanisms. This part of the project will identify individual EHV-1 proteins that are CTL target antigens and which Major Histocompatibility Complex (MHC) class I molecules present these antigens, focusing on two common MHC haplotypes that are found in approximately half of the Thoroughbred population. The proposal is based on cutting edge techniques and theories in viral immunology.