Peptides/MHC-I complexes and CD8+T cells

描述：（由申请人提供）临床和实验证据点 CD 8 + T细胞在免疫防御细胞内 病原体这些病原体中最主要的是那些负责艾滋病 大流行病、疟疾和肺结核。许多癌细胞的独特蛋白质， 以及朊病毒也可以被认为是细胞内病原体。到 帮助开发疫苗，促进对这些病原体的防御，我们正在 研究了热休克融合蛋白（Hsfp）对CD 8 T细胞的刺激作用， 应答Hsfp由重组分枝杆菌（BCG）57 kDa形成， 热休克蛋白，称为hsp 65，在其C-末端融合有“融合蛋白 配偶体”（多肽或大蛋白质结构域）。融合伙伴包含 当在抗原呈递（树突）细胞中切除时， 并与细胞的I类MHC分子结合，可以激活CD 8 T细胞。是 CD 8 T细胞疫苗的有效性可能取决于它们的能力， 刺激产生足够数量的强效记忆性CD 8 T细胞， 细胞，能够裂解展示非常少的同源肽-MHC的靶细胞 复合物，因为许多病毒感染的细胞和癌细胞具有低水平 MHC-I分子和一些同源肽的低拷贝数。我们将研究 Hsfp如何被树突状细胞（DC）摄取并被蛋白水解裂解， 这些过程如何受到DC行为的改性剂的影响，包括 双链RNA和其上模式识别受体的配体 细胞总体目标是帮助提供一个平台， 免疫策略导致强效记忆性CD 8 T细胞的产量增加 细胞

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.