The identification of peptide fragments contained within HIV viral proteins which can elicit T cell immune responses is a critical step in the development of HIV T cell vaccines. We have developed a combined experimental and computational approach to rapidly identify viral peptides which exhibit strong binding affinities for MHC Class I alleles in vitro. These peptides then provide a greatly reduced list of potential immunogenic peptides which can then be assayed for their ability to induce cytotoxic T cell responses. Initially the computational methods are used to eliminate all viral peptides whose conformations are incompatible with the protein binding site. The binding affinity of the remaining peptides are measured by a thermal denaturation experiment performed on the MHC Class I/peptide complex. Our approach can be used to scan the interactions between all possible HIV T cell epitopes which are presented in very low concententrations on the cell surface and therefore difficult to find by purification techniques.
We have developed an approach to identify potential immunogenic peptides which can then be targeted for further development as HIV T cell vaccines. The results of this research will give us a technology base that will provide us an opportunity to enter into collaborative efforts with pharmaceutical companies to develop HIV vaccines.
