BAA-APPLICATION OF HLA DATA TO DEVELOP & IMPROVE VACCINE

免疫T淋巴细胞识别外来抗原需要呈现短的蛋白质片段，称为多肽，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。数以千计的多肽来自细胞和病原体分子，在对感染或疫苗的免疫反应中出现，但只有一小部分被表征。目前的项目试图更详细地定义由特定的人类MHC I类分子(人类白细胞抗原-A、-B和~C)呈递的多肽。从人类免疫缺陷病毒-1(HIV-1)感染前后的人类细胞系中提取纯化的人类白细胞抗原分子中的多肽。将使用层析和质谱学生成比较肽图，以分离和排序释放的多肽。这一方法将提供有关人类免疫缺陷病毒(HIV)限制性人类T细胞可利用的潜在靶表位的广泛信息。将开发一个可搜索的T细胞配基数据库，作为关于人类白细胞抗原分子提出的多肽的综合信息来源。

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.