Simian immunodeficiency virus (SIV) infection of the rhesus macaque is the best animal model with which to study HIV infection of humans. It is becoming increasingly apparent that the cellular immune response plays a central role in defense against the AIDS virus. However, SIV-specific cellular immune responses are poorly understood, are difficult to quantify and these shortcomings have hindered progress towards the development of a vaccine. The long- term goal of these studies is to quantitate CTL and HTL responses in vaccinated, MHC-defined macaques. Few cytotoxic T cell (CTL) and helper T cell (HTL) epitopes have been well defined in the rhesus macaque. Quantitation of the CTL response induced by candidate vaccines is, therefore, currently nearly impossible. There are also only a limited number of SIV/HIV HTL epitopes mapped in the rhesus. Definition of CTL and HTL epitopes and their restricting MHC alleles will be important in MHC tetramer and gamma interferon ELISPOT analysis. These two methods offer the most quantitative means by which to determine the cellular immune response in vaccinated rhesus macaques. In the first specific aim of the proposal, CTL and HTL epitopes will be defined in SIV proteins and their restricting MHC class I and II alleles in a cohort of SIV-infected rhesus macaques which are long term nonprogressors. In the second specific aim, MHC class II tetramers will be produced to evaluate SIV-specific HTL responses in vaccinated animals. This proposal will define multiple new CTL and HTL epitopes and their restricting MHC alleles. Definition of these epitopes will be crucial to the quantitation of the cellular immune response to candidate vaccines in rhesus macaques.
