BAA-APPLICATION OF HLA DATA TO DEVELOP & IMPROVE VACCINE

免疫T淋巴细胞识别外来抗原需要提供称为肽的短蛋白片段，这些蛋白片段与主要组织相容性复合体（MHC）分子结合，作为T细胞受体的配体。在对感染或疫苗接种的免疫反应中，出现了来自细胞和病原体分子的数千种肽，但其中只有一小部分已被表征。目前的项目旨在非常详细地定义特定的人类MHC I类分子（HLA-A， -B和~C）所呈现的肽。从人类免疫缺陷病毒1 （HIV-1）感染前后的人类细胞系纯化的HLA分子中提取多肽。比较肽图将生成使用色谱和质谱分离和测序释放肽。这种方法将为hla限制性人T细胞对HIV的反应提供潜在目标表位的广泛信息。一个可搜索的T细胞配体数据库将被开发，作为HLA分子所呈现肽的综合信息来源。

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.