BAA-APPLICATION OF HLA DATA TO DEVELOP & IMPROVE VACCINE

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Recognition of foreign antigens by immune T lymphocytes requires the presentation of short protein segments, termed peptides, bound to major histocompatability complex (MHC) molecules that serve as ligands for T cell receptors. Thousands of peptides, derived from both cellular and pathogen molecules, are presented during an immune response to infection or vaccination, but only a small proportion of these have been characterized. The current project seeks to define in great detail the peptides presented by specific human MHC class I molecules (HLA-A, -B, and ~C). Peptides will be extracted from purified HLA molecules derived from human cell lines both before and after infection by human immunodeficiency virus-1 (HIV-1). Comparative peptide maps will be generated using chromatography and mass spectrometry to separate and sequence the released peptides. This approach will provide extensive information on the potential target epitopes available to HLA-restricted human T cells responding to HIV. A searchable T cell ligand database will be developed as a comprehensive source of information on peptides presented by HLA molecules.