The central goal of Project 1 is to identify peptide components from conserved regions of HIV-1 proteins which are capable of stimulating a specific, MHC class I-restricted cytotoxic T lymphocyte (CTL) response in man. This research builds upon the extensive experience of Project 1 scientists in identifying immunogenic peptides from viral and tumor antigens based on allele-specific binding motifs, binding affinity to class 1 molecules in vitro, and the ability to elicit primary CTL responses in human lymphocytes and HLA transgenic mice. This methodology will be applied to identifying putative CTL epitopes in internal and surface proteins of HIV-1. The initial focus of the research will be HLA- A2 peptides since this is the most frequently expressed allele in the general population. This work can be subsequently expanded to other alleles to provide broad population coverage. By creating a candidate pool of HIV-1-derived Cit peptides, Project 1 provides the essential foundation for further pep tide evaluation by Project 2 which will study peptide recognition by lymphocytes obtained from HIV-1 infected individuals. Thus, Project I contributes directly to the development of a peptide-based immunotherapeutic for AIDS which is the central focus of this Program.
| Newman, Mark J; Livingston, Brian; McKinney, Denise M et al. (2002) T-lymphocyte epitope identification and their use in vaccine development for HIV-1. Front Biosci 7:d1503-15 |
| Altfeld, M A; Livingston, B; Reshamwala, N et al. (2001) Identification of novel HLA-A2-restricted human immunodeficiency virus type 1-specific cytotoxic T-lymphocyte epitopes predicted by the HLA-A2 supertype peptide-binding motif. J Virol 75:1301-11 |
| Ishioka, G Y; Fikes, J; Hermanson, G et al. (1999) Utilization of MHC class I transgenic mice for development of minigene DNA vaccines encoding multiple HLA-restricted CTL epitopes. J Immunol 162:3915-25 |
| Brander, C; Goulder, P J; Luzuriaga, K et al. (1999) Persistent HIV-1-specific CTL clonal expansion despite high viral burden post in utero HIV-1 infection. J Immunol 162:4796-800 |
