Peptides/MHC-I complexes and CD8+T cells

肽/MHC-I 复合物和 CD8 T 细胞

• 批准号: 6627803
• 负责人: HERMAN N EISEN
• 金额: $ 27.51万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-07-07 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6627803
• 关键词: Bacillus Calmette Guerin vaccine; CD8 molecule; MHC class I antigen; T cell receptor; bacterial proteins; chimeric proteins; cytotoxic T lymphocyte; dendritic cells; genetically modified animals; green fluorescent proteins; heat shock proteins; immunologic memory; laboratory mouse; receptor binding; tissue /cell culture; vector vaccine

DESCRIPTION: (provided by applicant) Clinical and experimental evidence point to a critical role for CD8' T cells in immune defenses against intracellular pathogens. Foremost among these pathogens are those responsible for the AIDS pandemic, malaria, and tuberculosis. Distinctive proteins of many cancer cells, as well as prions, can also be considered to be intracellular pathogens. To help develop vaccines that promote defenses against these pathogens, we are studying some heat shock fusion proteins (Hsfp) that stimulate CD8 T cell responses. The Hsfp are formed from a recombinant mycobacterial (BCG) 57kDa heat shock protein, called hsp65, fused at its C-terminus with a "fusion partner" (a polypeptide or large protein domain). Fusion partners contain peptide sequences that, when excised in antigen-presenting (dendritic) cells and bound to the cells' class I MHC molecules, can activate CD8 T cells. It is likely that the effectiveness of CD8 T cell vaccines depends upon their ability to stimulate the production of a sufficient number of potent memory CD8 T cells, able to lyse target cells displaying very few cognate peptide-MHC complexes, because many virus-infected cells and cancer cells have low levels of MHC-I molecules and low copy numbers of some cognate peptides. We will study how Hsfp are taken into and proteolytically cleaved by dendritic cells (DC) and how these processes are affected by modifiers of DC behaviour, including double-stranded RNA and ligands for pattern-recognition receptors on these cells. The overall goal is to help provide a platform to aid in the development of immunization strategies leading to increased yields of potent memory CD8 T cells.

描述：（由申请人提供）临床和实验证据点