Virus-specific T lymphocytes play a central role in the immune response t HIV. We have previously describe a technique for major histocompatibility complex MHC) class I typing rhesus monkeys and an SIVmac gag peptide-specific, CD8+ CTL response in rhesus monkeys restricted by MHC class I molecule Manu-A*01+. In the proposed studies we will develop a technique for characterizing the MHC class II Dr alleles i rhesus monkeys and define HIV-1 envelope peptide-specific, DR- restricted CD4+ T lymphocyte response in this species. We will then employ this understanding of these peptide epitope-specific, CD8+ and CD4+ T cell responses explores a number of novel peptide-based strategies for vaccine-induced, AID virus-specific immunity. Specifically, we will: I. Characterize MHC class II DR alleles of rhesus monkeys and their presentation of HIV-1 envelope peptides to CD4+ T lymphocytes. II. Assess novel peptide based vaccine strategies in rhesus monkeys, including: A. Alpha 3-macroglobulin/peptide induction of CTL B. b7/CD28 costimulatory signaling in the augmentation of peptide vaccine-elicited CTL C. gp39 in eliciting CD4+ T cell immunity D. Peptide/mucosal adjuvant/microsphere immunization for the induction of CD4+ T cells.