Activated cytotoxic T lymphocytes (CTL) directly recognize and kill cells that are transformed or virus infected. The ability to clinically activate CTL to recognize self-tumor cells or virus infected cells would be a major advance in the treatment of cancer or virus infections such as HIV. However, activation of the immune system in the clinical setting will require an understanding of CTL-target cell recognition at the molecular level. Other than the qualitative requirement of foreign antigen and major histocompatibility complex (MHC) proteins, target cell components necessary for optimal CTL recognition have not been defined. The overall aim of this project is to more precisely define the ability of the MHC-peptide antigen complex to trigger CTL and to determine the role of receptor-ligand interactions in this process. We will do this by preparing uniform-MHC- peptide antigens (where the majority of the MHC has the same peptide associated with it) and examine the antigenicity of these protein structures both in vitro and in vivo. Our intent is to determine if lipid vesicles containing this uniform or high density MHC-peptide antigen will activate CTL in vivo alone or together with accessory type molecules. The long term goal is to use our understanding of receptor-ligand interactions (antigen dependent and independent) to design vaccines able to trigger a T lymphocyte response in vivo against specific tumor types or against a wide range of virus isolates.
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